Science.gov

Sample records for dose range 3-20

  1. Extended range radiation dose-rate monitor

    DOEpatents

    Valentine, Kenneth H.

    1988-01-01

    An extended range dose-rate monitor is provided which utilizes the pulse pileup phenomenon that occurs in conventional counting systems to alter the dynamic response of the system to extend the dose-rate counting range. The current pulses from a solid-state detector generated by radiation events are amplified and shaped prior to applying the pulses to the input of a comparator. The comparator generates one logic pulse for each input pulse which exceeds the comparator reference threshold. These pulses are integrated and applied to a meter calibrated to indicate the measured dose-rate in response to the integrator output. A portion of the output signal from the integrator is fed back to vary the comparator reference threshold in proportion to the output count rate to extend the sensitive dynamic detection range by delaying the asymptotic approach of the integrator output toward full scale as measured by the meter.

  2. Wide-range radiation dose monitor

    DOEpatents

    Kopp, M.K.

    1984-09-20

    A radiation dose-rate monitor is provided which operates in a conventional linear mode for radiation in the 0 to 0.5 R/h range and utilizes a nonlinear mode of operation for sensing radiation from 0.5 R/h to over 500 R/h. The nonlinear mode is achieved by a feedback circuit which adjusts the high voltage bias of the proportional counter, and hence its gas gain, in accordance with the amount of radiation being monitored. This allows compression of readout onto a single scale over the range of 0 to greater than 500 R/h without scale switching operations.

  3. Wide-range radiation dose monitor

    DOEpatents

    Kopp, Manfred K.

    1986-01-01

    A radiation dose-rate monitor is provided which operates in a conventional linear mode for radiation in the 0 to 0.5 R/h range and utilizes a nonlinear mode of operation for sensing radiation from 0.5 R/h to over 500 R/h. The nonlinear mode is achieved by a feedback circuit which adjusts the high voltage bias of the proportional counter, and hence its gas gain, in accordance with the amount of radiation being monitored. This allows compression of readout onto a single scale over the range of 0 to greater than 500 R/h without scale switching operations.

  4. Effective dose range for dental cone beam computed tomography scanners.

    PubMed

    Pauwels, Ruben; Beinsberger, Jilke; Collaert, Bruno; Theodorakou, Chrysoula; Rogers, Jessica; Walker, Anne; Cockmartin, Lesley; Bosmans, Hilde; Jacobs, Reinhilde; Bogaerts, Ria; Horner, Keith

    2012-02-01

    To estimate the absorbed organ dose and effective dose for a wide range of cone beam computed tomography scanners, using different exposure protocols and geometries. Two Alderson Radiation Therapy anthropomorphic phantoms were loaded with LiF detectors (TLD-100 and TLD-100 H) which were evenly distributed throughout the head and neck, covering all radiosensitive organs. Measurements were performed on 14 CBCT devices: 3D Accuitomo 170, Galileos Comfort, i-CAT Next Generation, Iluma Elite, Kodak 9000 3D, Kodak 9500, NewTom VG, NewTom VGi, Pax-Uni3D, Picasso Trio, ProMax 3D, Scanora 3D, SkyView, Veraviewepocs 3D. Effective dose was calculated using the ICRP 103 (2007) tissue weighting factors. Effective dose ranged between 19 and 368 μSv. The largest contributions to the effective dose were from the remainder tissues (37%), salivary glands (24%), and thyroid gland (21%). For all organs, there was a wide range of measured values apparent, due to differences in exposure factors, diameter and height of the primary beam, and positioning of the beam relative to the radiosensitive organs. The effective dose for different CBCT devices showed a 20-fold range. The results show that a distinction is needed between small-, medium-, and large-field CBCT scanners and protocols, as they are applied to different indication groups, the dose received being strongly related to field size. Furthermore, the dose should always be considered relative to technical and diagnostic image quality, seeing that image quality requirements also differ for patient groups. The results from the current study indicate that the optimisation of dose should be performed by an appropriate selection of exposure parameters and field size, depending on the diagnostic requirements. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. {alpha}/{beta} ratio: A dose range dependence study

    SciTech Connect

    Garcia, Lourdes M. . E-mail: logarcia@ottawahospital.on.ca; Wilkins, David E.; Raaphorst, Gijsbert P.

    2007-02-01

    Purpose: To investigate the dependence of the {alpha}/{beta} ratio determined from in vitro survival curves on the dose ranges. Methods: Detailed clonogenic cell survival experiments were used to determine the least squares estimators for the linear quadratic model for different dose ranges. The cell lines used were CHO AA8, a Chinese hamster fibroblast cell line; U-373 MG, a human glioblastoma cell line; and CP3 and DU-145, two human prostate carcinoma cell lines. The {alpha}, {beta}, and {alpha}/{beta} ratio behaviors, combined with a goodness-of-fit analysis and Monte Carlo simulation of the experiments, were assessed within different dose regions. Results: Including data from the low-dose region has a significant influence on the determination of the {alpha}, {beta}, and {alpha}/{beta} ratio from in vitro survival curve data. In this region, the values are poorly determined and have significant variability. The mid-dose region is characterized by more precise and stable values and is in agreement with the linear quadratic model. The high-dose region shows relatively small statistical error in the fitted parameters but the goodness-of-fit and Monte Carlo analyses showed poor quality fits. Conclusion: The dependence of the fitted {alpha} and {beta} on the dose range has an impact on the {alpha}/{beta} ratio determined from the survival data. The low-dose region had a significant influence that could be a result of a strong linear, rather than quadratic, component, hypersensitivity, and adaptive responses. This dose dependence should be interpreted as a caution against using inadequate in vitro cell survival data for {alpha}/{beta} ratio determination.

  6. Analytical probabilistic proton dose calculation and range uncertainties

    NASA Astrophysics Data System (ADS)

    Bangert, M.; Hennig, P.; Oelfke, U.

    2014-03-01

    We introduce the concept of analytical probabilistic modeling (APM) to calculate the mean and the standard deviation of intensity-modulated proton dose distributions under the influence of range uncertainties in closed form. For APM, range uncertainties are modeled with a multivariate Normal distribution p(z) over the radiological depths z. A pencil beam algorithm that parameterizes the proton depth dose d(z) with a weighted superposition of ten Gaussians is used. Hence, the integrals ∫ dz p(z) d(z) and ∫ dz p(z) d(z)2 required for the calculation of the expected value and standard deviation of the dose remain analytically tractable and can be efficiently evaluated. The means μk, widths δk, and weights ωk of the Gaussian components parameterizing the depth dose curves are found with least squares fits for all available proton ranges. We observe less than 0.3% average deviation of the Gaussian parameterizations from the original proton depth dose curves. Consequently, APM yields high accuracy estimates for the expected value and standard deviation of intensity-modulated proton dose distributions for two dimensional test cases. APM can accommodate arbitrary correlation models and account for the different nature of random and systematic errors in fractionated radiation therapy. Beneficial applications of APM in robust planning are feasible.

  7. Upgrading NASA/DOSE laser ranging system control computers

    NASA Technical Reports Server (NTRS)

    Ricklefs, Randall L.; Cheek, Jack; Seery, Paul J.; Emenheiser, Kenneth S.; Hanrahan, William P., III; Mcgarry, Jan F.

    1993-01-01

    Laser ranging systems now managed by the NASA Dynamics of the Solid Earth (DOSE) and operated by the Bendix Field Engineering Corporation, the University of Hawaii, and the University of Texas have produced a wealth on interdisciplinary scientific data over the last three decades. Despite upgrades to the most of the ranging station subsystems, the control computers remain a mix of 1970's vintage minicomputers. These encompass a wide range of vendors, operating systems, and languages, making hardware and software support increasingly difficult. Current technology allows replacement of controller computers at a relatively low cost while maintaining excellent processing power and a friendly operating environment. The new controller systems are now being designed using IBM-PC-compatible 80486-based microcomputers, a real-time Unix operating system (LynxOS), and X-windows/Motif IB, and serial interfaces have been chosen. This design supports minimizing short and long term costs by relying on proven standards for both hardware and software components. Currently, the project is in the design and prototyping stage with the first systems targeted for production in mid-1993.

  8. Butaclamol in newly admitted chronic schizophrenic patients: a modified fixed-dose dose-range design.

    PubMed

    Clark, M L; Costiloe, J P; Wood, F; Paredes, A; Fulkerson, F G

    1977-11-01

    In a double-blind placebo controlled study of newly admitted chronic schizophrenics, an attempt was made to further evaluate the safety, acceptability, and effectiveness of BT in doses of 10, 20, and 40 mg. Significant dose related responses occurred on several behavioral variables by the first week of treatment. Maximum clinical response appeared to be at the 20-40 mg. dose level. Extrapyramidal signs occurred at all doses, but with greater severity at higher doses. Excessive daytime drowsiness occurred in all groups but with longer duration and greater intensity in the 20 mg. group. Rebound insomnia occurred after the abrupt withdrawal of BT at all dose levels suggesting the desirability of further study of its hypnotic properties.

  9. Four Week Oral (Gavage) Dose Range-Finding Study of Halofantrine Hydrochloride in Mice

    DTIC Science & Technology

    1994-10-26

    Because marginal halofantrine- induced toxicity was seen in low dose females, the following dose level ranges are suggested: 1 - 2, 4 - 8 and 15-30 mg/kg...halofantrine- induced toxicity was seen in low dose females, the following dose level ranges are suggested: 1 - 2, 4 - 8 and 15-30 mg/kg/day. 2...selected on the basis of Sponsor-supplied subchronic toxicity data in rats and following discussions with the Sponsor. During the test animal selection

  10. Lung tumor induction in mice: neutron RBE at low doses. [0-50 rad range

    SciTech Connect

    Ullrich, R.L.

    1982-01-01

    Experimental studies have demonstrated that neutrons are more tumorigenic on a dose for dose basis than are gamma rays. However, recent studies examining dose-response relationships and dose rate or fractionation effects have served to emphasize inadequacies in our understanding of neutron carcinogenesis. These studies have demonstrated that the dose-response curves bend over at relatively low doses. This results in a dose response curve which has a convex upward form over the 20 to 240 rad dose range. Further, it has been demonstrated that the life shortening and tumorigenic response after fractionated or protracted neutron exposure is increased in this 20 to 240 rad dose range. Since the dose response is bending over in this dose range it is of importance to obtain information at lower doses. Experiments are being conducted on tumor induction with neutrons emphasizing the effects of neutrons in the 0 to 50 rad dose range on the induction of lung adenocarcinomas and mammary adenocarcinomas in BALB/c mice. Current data on the induction of lung adenocarcinomas after neutron or gamma ray irradiation and their implications for estimates of risk for neutron exposures at low doses are described. (ERB)

  11. Sibutramine in weight control: a dose-ranging, efficacy study.

    PubMed

    Weintraub, M; Rubio, A; Golik, A; Byrne, L; Scheinbaum, M L

    1991-09-01

    We tested the safety and efficacy of sibutramine, 5 and 20 mg, and placebo on weight loss. Medication was added to caloric restriction, behavior modification, and exercise in a parallel-group, double-blind clinical trial. Participants were 130% to 180% of ideal body weight and in good health. The study lasted 12 weeks over Thanksgiving, Christmas, and New Year's Day. Weight loss during 8 weeks of study medication was: placebo, 1.4 +/- 2.1 kg (n = 19); 5 mg sibutramine, 2.9 +/- 2.3 kg (n = 18); and 20 mg sibutramine, 5.0 +/- 2.7 kg (n = 18) (p less than 0.05 sibutramine, 5 and 20 mg, versus placebo; p less than 0.05 sibutramine, 20 mg versus 5 mg). There is a significant dose-effect relationship. Five participants left the study before completion, all because of adverse events; placebo (one patient), 5 mg sibutramine (one patient), and 20 mg sibutramine (three patients). Sleep difficulties were noted by eight participants (20 mg sibutramine, seven patients; 5 mg, one patient; and placebo, no patients). Six of 21 participants receiving 20 mg complained of irritability, unusual impatience, or "excitation." Sibutramine, 5 and 20 mg, added to a multimodal program assisted participants in losing weight.

  12. Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria.

    PubMed

    Hew, M; Gillman, A; Sutherland, M; Wark, P; Bowden, J; Guo, M; Reddel, H K; Jenkins, C; Marks, G B; Thien, F; Rimmer, J; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Wright, C; Bint, M; Yozghatlian, V; Burgess, S; Sivakumaran, P; Yan, K Y; Kritikos, V; Peters, M; Baraket, M; Aminazad, A; Robinson, P; Jaffe, A; Powell, H; Upham, J W; McDonald, V M; Gibson, P G

    2016-11-01

    Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1 ) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1 . Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range

  13. Dose range-finding studies with frovatriptan in the acute treatment of migraine.

    PubMed

    Rapoport, Alan; Ryan, Robert; Goldstein, Jerome; Keywood, Charlotte

    2002-04-01

    To determine the optimum dose of frovatriptan for the acute treatment of migraine. Frovatriptan is a new triptan developed for the acute treatment of migraine. The dose-response characteristics and safety of frovatriptan have been investigated across a broad range of doses from 0.5 to 40 mg. Two randomized, placebo-controlled, double-blind, parallel-group trials, with a total of 1453 patients, were performed to determine the optimal dose of the 5-HT(B/1D)agonist, frovatriptan, for the acute treatment of migraine. The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg in the low-dose study. At 2 hours postdosing for initial moderate or severe headache (International Headache Society grades 2 or 3), there was an approximate two-fold difference in the proportion of patients taking frovatriptan doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours postdose, and 2.5 mg was identified as the lowest effective dose for the relief of migraine and accompanying symptoms. Above 2.5 mg, no dose-response relationship was observed for any efficacy parameters. There was an increase in the incidence of adverse events from 10 mg and above, but the vast majority were rated as mild in severity and did not impact upon tolerability in a significant manner. Frovatriptan was well tolerated throughout the dose range of 0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and tolerability for the acute treatment of migraine.

  14. Experimental study and mathematical modeling of the behavior of St.3, 20Kh13, and 08Kh18N10T steels in wide ranges of strain rates and temperatures

    NASA Astrophysics Data System (ADS)

    Bragov, A. M.; Igumnov, L. A.; Kaidalov, V. B.; Konstantinov, A. Yu.; Lapshin, D. A.; Lomunov, A. K.; Mitenkov, F. M.

    2015-11-01

    Results of an experimental study of the behavior of St.3, 20Kh13, and 08Kh18N10T steels under static and dynamic loading are reported. The influence of the strain rate and temperature on characteristics of strength and plasticity is studied. Based on the data obtained, the parameters of the Johnson-Cook model are determined. This model is used in commercial software to describe the yield surface radius as a function of loading parameters. The adequacy of the identified model is verified in a series of special test experiments.

  15. New method of proportional counter feedback biasing for wide-range radiation dose-rate monitors

    SciTech Connect

    Kopp, M.K.; Valentine, K.H.; Guerrant, G.C.; Manning, F.W.

    1984-01-01

    A prototypic wide-range radiation dose-rate monitor for civil defense applications has been developed and tested. The specified dose-rate range (0 to 500 R/h) was displayed on a single readout scale by using feedback-controlled biasing of a proportional counter. This new method is based on controlling the avalanche multiplication factor (gas gain) of the counter by varying its bias voltage in response to its measured output current (i.e., detected dose rate). The counter output current varies between 0 and 1.5 nA in a quasi-logarithmic response to dose rates between 0 and 500 R/h. The corresponding values of gas gain and bias voltage range from 1 to 300 and 200 to 1900 V respectively.

  16. NOTE: Study of Gafchromic® EBT film response over a large dose range

    NASA Astrophysics Data System (ADS)

    Martišíková, Mária; Jäkel, Oliver

    2010-05-01

    Presently Gafchromic EBT films are widely used for relative dose verification in standard radiation therapy using high-energy photons, inclusive IMRT. The use of films for dosimetry in medical ion beams is more complicated due to the strongly inhomogeneous dose deposition by ions on microscopic level. Track structure models, presently used to describe dosimeter response as a function of the ion field properties, are based on input information which can be obtained from the film response in photon beams. We therefore studied the performance of Gafchromic EBT films, ancestors of currently available EBT2 films, in 60Co photon beams. The dose-response curve was measured from 7.5 × 10-2 Gy to 3 × 104 Gy. The dynamic range, linearity and dose rate dependence of this calibration curve were studied. A high saturation dose of 3 × 103 Gy, and thus a large dynamic range, was observed. No signs of supralinearity and bleaching due to radiation were found. No dependence of the response on the dose rate at high dose rates and high doses was found. All those properties justify the use of simplified models of the film response to ions. Furthermore, fits of the calibration data by predictions of different models for signal creation mechanism of dosimetric materials were performed. The best description was found for the recently published gamma-distributed single-hit model which takes into account different sizes of the active centres.

  17. Dose Uncertainties in IMPT for Oropharyngeal Cancer in the Presence of Anatomical, Range, and Setup Errors

    SciTech Connect

    Kraan, Aafke C.; Water, Steven van de; Teguh, David N.; Al-Mamgani, Abrahim; Madden, Tom; Kooy, Hanne M.; Heijmen, Ben J.M.; Hoogeman, Mischa S.

    2013-12-01

    Purpose: Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions. Methods and Materials: We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation. Results: For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust. Conclusions: For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive

  18. Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

    NASA Astrophysics Data System (ADS)

    Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

    2014-08-01

    The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be

  19. Feasibility of RACT for 3D dose measurement and range verification in a water phantom

    SciTech Connect

    Alsanea, Fahed; Moskvin, Vadim; Stantz, Keith M.

    2015-02-15

    Purpose: The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Methods: Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). Results: The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error < 150 μm) for a 1 cGy Bragg peak dose, where the integral dose within the Bragg peak was measured to within 2%. For existing hydrophone detector sensitivities, a Bragg peak dose of 1.6 cGy is possible. Conclusions: This study demonstrates that computed tomographic scanner based on ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly

  20. Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

    PubMed Central

    Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

    2014-01-01

    The purpose of this study was to investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for 7 disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head & neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and Monte Carlo algorithms to obtain the average range differences (ARD) and root mean square deviation (RMSD) for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation (ADD) of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing Monte Carlo dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head & neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head & neck treatments. We conclude that currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific

  1. Dosimetric evaluation of sucrose and granulated cane sugar in the therapeutic dose range

    SciTech Connect

    Davidson, Melanie T. M.; Jordan, Kevin J.

    2009-04-15

    Granulated cane sugar has been used as a dosimetric material to report dose in high dose accidental irradiations. The purpose of this study was to assess whether clinical dosimetry is also plausible with such a commonly available material. The behavior of cane sugar was explored with respect to therapeutically relevant radiation quantities (dose, dose rate) and qualities (energy, radiation type) as well as under different temperature conditions. The stability of the signal postirradiation was also measured. Absorbed dose was measured by spectrophotometric readout of a ferrous ammonium sulfate xylenol orange (FX)-sugar solution in 10 cm path length cells. A visible color change was produced as a function of dose when the irradiated sugar samples were dissolved in FX solution (10% dilution by mass). A comparison of the optical absorbance spectra and dose response of cane sugar with analytical grade sucrose was done to establish a benchmark standard from which subsequent dosimetry measurements can be validated. The response of the sugar dosimeter read at 590 nm was found to be linear over the dose range of 100-2000 cGy, independent of energy (6-18 MV) and of the average dose rate (100-500 cGy/min). The readout of sugar samples irradiated with mixed photon and electron fields was also shown to be independent of radiation type (photons and electrons). Sugar temperature (20-40 degree sign C) during irradiation did not affect dose estimates, making it a promising dosimeter for in vivo dosimetry, particularly in cases where the dosimeter must remain in contact with the patient for an extended period of time. Sugar can be used as an integrating dosimeter, since it exhibits no fractionation effects. Granulated cane sugar is cost effective, safe, soft tissue equivalent, and can be used under various experimental conditions, making it a suitable dosimeter for some radiotherapy applications.

  2. Dosimetric evaluation of sucrose and granulated cane sugar in the therapeutic dose range.

    PubMed

    Davidson, Melanie T M; Jordan, Kevin J

    2009-04-01

    Granulated cane sugar has been used as a dosimetric material to report dose in high dose accidental irradiations. The purpose of this study was to assess whether clinical dosimetry is also plausible with such a commonly available material. The behavior of cane sugar was explored with respect to therapeutically relevant radiation quantities (dose, dose rate) and qualities (energy, radiation type) as well as under different temperature conditions. The stability of the signal postirradiation was also measured. Absorbed dose was measured by spectrophotometric readout of a ferrous ammonium sulfate xylenol orange (FX)-sugar solution in 10 cm path length cells. A visible color change was produced as a function of dose when the irradiated sugar samples were dissolved in FX solution (10% dilution by mass). A comparison of the optical absorbance spectra and dose response of cane sugar with analytical grade sucrose was done to establish a benchmark standard from which subsequent dosimetry measurements can be validated. The response of the sugar dosimeter read at 590 nm was found to be linear over the dose range of 100-2000 cGy, independent of energy (6-18 MV) and of the average dose rate (100-500 cGy/min). The readout of sugar samples irradiated with mixed photon and electron fields was also shown to be independent of radiation type (photons and electrons). Sugar temperature (20-40 degrees C) during irradiation did not affect dose estimates, making it a promising dosimeter for in vivo dosimetry, particularly in cases where the dosimeter must remain in contact with the patient for an extended period of time. Sugar can be used as an integrating dosimeter, since it exhibits no fractionation effects. Granulated cane sugar is cost effective, safe, soft tissue equivalent, and can be used under various experimental conditions, making it a suitable dosimeter for some radiotherapy applications.

  3. Lithium fluoride detectors for recording gamma rays over a wide dose range

    SciTech Connect

    Erkin, V.G.; Persinen, A.A.

    1987-02-01

    The authors have combined thermoluminescent and spectrophotometric methods to measure doses in the range 1 x 10/sup -4/ to 6 x 10/sup 5/ Gy with DTG-4 detectors of diameter 5 mm and thickness 1 mm. We used a /sup 60/Co or /sup 137/Cs source (doses 10/sup -4/-10 Gy), as well as an MRKh-..gamma..-20 apparatus (doses of 10/sup 2/-6 x 10/sup 5/ Gy). The gamma doses were monitored with a set of ionization chambers in the VA-J-18 apparatus as well as with ferrous sulfate dosemeters. The light sum was recorded over the range 20-200/sup 0/C with a Harshaw model 2000-D instrument and with a KDT-1. The optical absorption spectra were measured with an SF-26 spectrophotometer over the range 200-600 nm. The detectors were irradiated in batches of five for each dose in plastic cassettes providing obedience to the electron-equilibrium conditions.

  4. The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

    SciTech Connect

    Liebl, Jakob; Paganetti, Harald; Zhu, Mingyao; Winey, Brian A.

    2014-09-15

    Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions

  5. 47 CFR 3.20 - Application form.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AUTHORITIES IN MARITIME AND MARITIME MOBILE-SATELLITE RADIO SERVICES Application Procedures § 3.20 Application form. Written application must be made to the Federal Communications Commission on FCC Form 44... 47 Telecommunication 1 2010-10-01 2010-10-01 false Application form. 3.20 Section 3.20...

  6. Measurement of a wide-range of X-ray doses using specialty doped silica fibres

    NASA Astrophysics Data System (ADS)

    Abdul Sani, S. F.; Hammond, R.; Jafari, S. M.; Wahab, Norfadira; Amouzad Mahdiraji, G.; Siti Shafiqah, A. S.; Abdul Rashid, H. A.; Maah, M. J.; Aldousari, H.; Alkhorayef, M.; Alzimami, M.; Bradley, D. A.

    2017-08-01

    Using six types of tailor-made doped optical fibres, we carry out thermoluminescent (TL) studies of X-rays, investigating the TL yield for doses from 20 mGy through to 50 Gy. Dosimetric parameters were investigated for nominal 8 wt% Ge doped fibres that in two cases were co-doped, using B in one case and Br in the other. A comparative measurement of surface analysis has also been made for non-annealed and annealed capillary fibres, use being made of X-ray Photoelectron Spectroscopy (XPS) analysis. Comparison was made with the conventional TL phosphor LiF in the form of the proprietary product TLD-100, including dose response and glow curves investigated for X-rays generated at 60 kVp over a dose range from 2 cGy to 50 Gy. The energy response of the fibres was also performed for X-rays generated at peak accelerating potentials of 80 kVp, 140 kVp, 250 kVp and 6 MV photons for an absorbed dose of 2 Gy. Present results show the samples to be suitable for use as TL dosimeters, with good linearity of response and a simple glow curve (simple trap) distribution. It has been established that the TL performance of an irradiated fibre is not only influenced by radiation parameters such as energy, dose-rate and total dose but also the type of fibre.

  7. Dynamic dose assessment by Large Eddy Simulation of the near-range atmospheric dispersion.

    PubMed

    Vervecken, Lieven; Camps, Johan; Meyers, Johan

    2015-03-01

    In order to improve the simulation of the near-range atmospheric dispersion of radionuclides, computational fluid dynamics is becoming increasingly popular. In the current study, Large-Eddy Simulation is used to examine the time-evolution of the turbulent dispersion of radioactive gases in the atmospheric boundary layer, and it is coupled to a gamma dose rate model that is based on the point-kernel method with buildup factors. In this way, the variability of radiological dose rate from cloud shine due to instantaneous turbulent mixing processes can be evaluated. The steady release in an open field of (41)Ar and (133)Xe for 4 different release heights is studied, thus covering radionuclides that decay with a high-energy gamma and a low-energy gamma, respectively. Based on these simulations, the variability of dose rates at ground level for different averaging times in the dose measurements is analyzed. It is observed that turbulent variability in the wind field can lead to dose estimates that are underestimated by up to a factor of four when conventional long-term measurements are used to estimate the dose from short-term exposures.

  8. Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers: a double-blind, randomized, dose-ranging study.

    PubMed

    Wohlfarth, K; Schwandt, I; Wegner, F; Jürgens, T; Gelbrich, G; Wagner, A; Bogdahn, U; Schulte-Mattler, W

    2008-12-01

    Despite extensive clinical experience and published data regarding botulinum toxin, questions remain about the clinical substitution of one botulinum toxin formulation for another. In the case of Dysport and Botox, dose-equivalence ratios ranging from 1:1 to 6:1 (Dysport:Botox) have been advocated. This dose-ranging, electroneurographic study investigated the dose equivalence, diffusion characteristics (spread) and safety of these two type-A toxins in 79 volunteers. Dysport and Botox caused significant and similar reductions in compound muscle action potential (CMAP) amplitude in the target muscle (extensor digitorum brevis, EDB) 2 weeks after injection, with effects persisting to the 12-week timepoint. For both products, the reduction in amplitude was increased with increasing doses and with increasing concentration. The effects of toxin on neighbouring muscles were much smaller and of a shorter duration than those on the target muscle, implying a modest spread of toxin. Unlike the target muscle, the effects were greater with the higher volume, suggesting this volume led to greater diffusion from the EDB. No adverse events were reported. Statistical modelling with CMAP amplitude data from the target muscle gave a bioequivalence of 1.57 units of Dysport:1 unit of Botox (95 % CI: 0.77-3.20 units). The data indicate that a dose-equivalence ratio of 3:1 was within the statistical error limits, but ratios over 3:1 are too high.

  9. Optimum organ volume ranges for organs at risk dose in cervical cancer intracavitary brachytherapy

    PubMed Central

    Siavashpour, Zahra; Aghamiri, Mahmoud Reza; Manshadi, Hamid Reza Dehghan; Ghaderi, Reza; Kirisits, Christian

    2016-01-01

    Purpose To analyze the optimum organ filling point for organs at risk (OARs) dose in cervical cancer high-dose-rate (HDR) brachytherapy. Material and methods In a retrospective study, 32 locally advanced cervical cancer patients (97 insertions) who were treated with 3D conformal external beam radiation therapy (EBRT) and concurrent chemotherapy during 2010-2013 were included. Rotterdam HDR tandem-ovoid applicators were used and computed tomography (CT) scanning was performed after each insertion. The OARs delineation and GEC-ESTRO-based clinical target volumes (CTVs) contouring was followed by 3D forward planning. Then, dose volume histogram (DVH) parameters of organs were recorded and patients were classified based on their OARs volumes, as well as their inserted tandem length. Results The absorbed dose to point A ranged between 6.5-7.5 Gy. D0.1cm3 and D2cm3 of the bladder significantly increased with the bladder volume enlargement (p value < 0.05). By increasing the bladder volume up to about 140 cm3, the rectum dose was also increased. For the cases with bladder volumes higher than 140 cm3, the rectum dose decreased. For bladder volumes lower than 75 cm3, the sigmoid dose decreased; however, for bladder volumes higher than 75 cm3, the sigmoid dose increased. The D2cm3 of the bladder and rectum were higher for longer tandems than for shorter ones, respectively. The divergence of the obtained results for different tandem lengths became wider by the extension of the bladder volume. The rectum and sigmoid volume had a direct impact on increasing their D0.1cm3 and D2cm3, as well as decreasing their D10, D30, and D50. Conclusions There is a relationship between the volumes of OARs and their received doses. Selecting a bladder with a volume of about 70 cm3 or less proved to be better with regards to the dose to the bladder, rectum, and sigmoid. PMID:27257418

  10. Detectors for in vivo range and dose verification in proton therapy

    NASA Astrophysics Data System (ADS)

    Alarcon, R.; Blyth, D.; Galyaev, E.; Holmes, J.; Ice, L.; Randall, G.; Bues, M.; Fatyga, M.

    2016-09-01

    Particle detection instrumentation to address the in vivo verifications of proton dose and range is under development as part of a proton therapy research program focused on patient quality assurance. For in vivo proton range verification, a collimated gamma detector array is under construction to indirectly measure the position of the Bragg peak for each proton beam spot to within 1-2 mm precision. For dose flux verification, a proton fluence detector based on the technology of the Micromegas is under construction. This detector has an active area of about 100 cm2, coordinate resolution of better than 1 mm, and handling of incident proton beam fluxes of 109-1013 particles/s.

  11. A Dose-Ranging Study of a Methylphenidate Transdermal System in Children with ADHD

    ERIC Educational Resources Information Center

    Pelham, William E.; Manos, Michael J.; Ezzell, Cora E.; Tresco, Katy E.; Gnagy, Elizabeth M.; Hoffman, Martin T.; Onyango, Adia N.; Fabiano, Gregory A.; Lopez-Williams, Andy; Wymbs, Brian T.; Caserta, Donald; Chronis, Andrea M.; Burrows-MacLean, Lisa; Morse, Gene

    2005-01-01

    Objective: This was a multicenter, double-blind, randomized, dose-ranging study of a methylphenidate (MPH) transdermal system (MTS). Medication (placebo, 0.45, 0.9, and 1.8 mg/h) was crossed with application time (6 a.m., 7 a.m.) to evaluate MTS efficacy and influence of exposure time on morning effects. Method: The study took place in a summer…

  12. New Morphine Analogs Produce Peripheral Antinociception within a Certain Dose Range of Their Systemic Administration.

    PubMed

    Lackó, Erzsébet; Riba, Pál; Giricz, Zoltán; Váradi, András; Cornic, Laura; Balogh, Mihály; Király, Kornél; Csekő, Kata; Mousa, Shaaban A; Hosztafi, Sándor; Schäfer, Michael; Zádori, Zoltán Sándor; Helyes, Zsuzsanna; Ferdinandy, Péter; Fürst, Susanna; Al-Khrasani, Mahmoud

    2016-10-01

    Growing data support peripheral opioid antinociceptive effects, particularly in inflammatory pain models. Here, we examined the antinociceptive effects of subcutaneously administered, recently synthesized 14-O-methylmorphine-6-O-sulfate (14-O-MeM6SU) compared with morphine-6-O-sulfate (M6SU) in a rat model of inflammatory pain induced by an injection of complete Freund's adjuvant and in a mouse model of visceral pain evoked by acetic acid. Subcutaneous doses of 14-O-MeM6SU and M6SU up to 126 and 547 nmol/kg, respectively, produced significant and subcutaneous or intraplantar naloxone methiodide (NAL-M)-reversible antinociception in inflamed paws compared with noninflamed paws. Neither of these doses significantly affected thiobutabarbital-induced sleeping time or rat pulmonary parameters. However, the antinociceptive effects of higher doses were only partially reversed by NAL-M, indicating contribution of the central nervous system. In the mouse writhing test, 14-O-MeM6SU was more potent than M6SU after subcutaneous or intracerebroventricular injections. Both displayed high subcutaneous/intracerebroventricular ED50 ratios. The antinociceptive effects of subcutaneous 14-O-MeM6SU and M6SU up to 136 and 3043 nmol/kg, respectively, were fully antagonized by subcutaneous NAL-M. In addition, the test compounds inhibited mouse gastrointestinal transit in antinociceptive doses. Taken together, these findings suggest that systemic administration of the novel compound 14-O-MeM6SU similar to M6SU in specific dose ranges shows peripheral antinociception in rat and mouse inflammatory pain models without central adverse effects. These findings apply to male animals and must be confirmed in female animals. Therefore, titration of systemic doses of opioid compounds with limited access to the brain might offer peripheral antinociception of clinical importance.

  13. Investigation of Kodak extended dose range (EDR) film for megavoltage photon beam dosimetry.

    PubMed

    Chetty, Indrin J; Charland, Paule M

    2002-10-21

    We have investigated the dependence of the measured optical density on the incident beam energy, field size and depth for a new type of film, Kodak extended dose range (Kodak EDR). Film measurements have been conducted over a range of field sizes (3 x 3 cm2 to 25 x 25 cm2) and depths (d(max) to 15 cm), for 6 MV and 15 MV photons within a solid water phantom, and the variation in sensitometric response (net optical density versus dose) has been reported. Kodak EDR film is found to have a linear response with dose, from 0 to 350 cGy, which is much higher than that typically seen for Kodak XV film (0-50 cGy). The variation in sensitometric response for Kodak EDR film as a function of field size and depth is observed to be similar to that of Kodak XV film; the optical density varied in the order of 2-3% for field sizes of 3 x 3 cm2 and 10 x 10 cm2 at depths of d(max), 5 cm and 15 cm in the phantom. Measurements for a 25 x 25 cm2 field size showed consistently higher optical densities at depths of d(max), 5 cm and 15 cm, relative to a 10 x 10 cm2 field size at 5 cm depth, with 4-5% differences noted at a depth of 15 cm. Fractional depth dose and profiles conducted with Kodak EDR film showed good agreement (2%/2 mm) with ion chamber measurements for all field sizes except for the 25 x 25 cm2 at depths greater than 15 cm, where differences in the order of 3-5% were observed. In addition, Kodak EDR film measurements were found to be consistent with those of Kodak XV film for all fractional depth doses and profiles. The results of this study indicate that Kodak EDR film may be a useful tool for relative dosimetry at higher dose ranges.

  14. Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis.

    PubMed

    Rosenthal, Ian M; Tasneen, Rokeya; Peloquin, Charles A; Zhang, Ming; Almeida, Deepak; Mdluli, Khisimuzi E; Karakousis, Petros C; Grosset, Jacques H; Nuermberger, Eric L

    2012-08-01

    In previous experiments, replacing the 10-mg/kg of body weight daily dose of rifampin with 7.5 to 10 mg/kg of rifapentine in combinations containing isoniazid and pyrazinamide reduced the duration of treatment needed to cure tuberculosis in BALB/c mice by approximately 50% due to rifapentine's more potent activity and greater drug exposures obtained. In the present study, we performed dose-ranging comparisons of the bactericidal and sterilizing activities of rifampin and rifapentine, alone and in combination with isoniazid and pyrazinamide with or without ethambutol, in BALB/c mice and in C3HeB/FeJ mice, which develop necrotic lung granulomas after infection with Mycobacterium tuberculosis. Each rifamycin demonstrated a significant increase in sterilizing activity with increasing dose. Rifapentine was roughly 4 times more potent in both mouse strains. These results reinforce the rationale for ongoing clinical trials to ascertain the highest well-tolerated doses of rifampin and rifapentine. This study also provides an important benchmark for the efficacy of the first-line regimen in C3HeB/FeJ mice, a strain in which the lung lesions observed after M. tuberculosis infection may better represent the pathology of human tuberculosis.

  15. Dose-Ranging Comparison of Rifampin and Rifapentine in Two Pathologically Distinct Murine Models of Tuberculosis

    PubMed Central

    Rosenthal, Ian M.; Tasneen, Rokeya; Peloquin, Charles A.; Zhang, Ming; Almeida, Deepak; Mdluli, Khisimuzi E.; Karakousis, Petros C.; Grosset, Jacques H.

    2012-01-01

    In previous experiments, replacing the 10-mg/kg of body weight daily dose of rifampin with 7.5 to 10 mg/kg of rifapentine in combinations containing isoniazid and pyrazinamide reduced the duration of treatment needed to cure tuberculosis in BALB/c mice by approximately 50% due to rifapentine's more potent activity and greater drug exposures obtained. In the present study, we performed dose-ranging comparisons of the bactericidal and sterilizing activities of rifampin and rifapentine, alone and in combination with isoniazid and pyrazinamide with or without ethambutol, in BALB/c mice and in C3HeB/FeJ mice, which develop necrotic lung granulomas after infection with Mycobacterium tuberculosis. Each rifamycin demonstrated a significant increase in sterilizing activity with increasing dose. Rifapentine was roughly 4 times more potent in both mouse strains. These results reinforce the rationale for ongoing clinical trials to ascertain the highest well-tolerated doses of rifampin and rifapentine. This study also provides an important benchmark for the efficacy of the first-line regimen in C3HeB/FeJ mice, a strain in which the lung lesions observed after M. tuberculosis infection may better represent the pathology of human tuberculosis. PMID:22664964

  16. Range of Effective Corticosteroid Doses for Alleviating Dyspnea in Terminal Cancer Patients: A Retrospective Review.

    PubMed

    Maeda, Tsuyoshi; Hayakawa, Toru

    2017-03-01

    This study aimed to determine the range of mean cumulative corticosteroid doses that could effectively palliate dyspnea in opioid-treated patients with terminal cancer and to investigate the demographic or biochemical factors predictive of corticosteroid responsiveness. To this end, responders and nonresponders were compared with regard to corticosteroid dose and whether they had initiated opioid use before or concomitantly with corticosteroid use. A logistic regression analysis was conducted to assess the impacts of demographic and biochemical factors on corticosteroid effectiveness. The final sample comprised 20 patients who satisfied the selection criteria. The responders accounted for 70% of the total sample (n = 14) and experienced the strongest effect with regard to dyspnea palliation at a mean cumulative dose equivalent to 64.4 mg prednisolone. However, no factors predictive of response were identified. In summary, this retrospective study identified effective corticosteroid doses for dyspnea alleviation in terminal cancer patients. Although our study sample was limited in size, the results support further prospective research.

  17. 47 CFR 3.20 - Application form.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AUTHORITIES IN MARITIME AND MARITIME MOBILE-SATELLITE RADIO SERVICES Application Procedures § 3.20 Application form. Written application must be made to the Federal Communications Commission on FCC Form 44... 47 Telecommunication 1 2011-10-01 2011-10-01 false Application form. 3.20 Section...

  18. Range and modulation dependencies for proton beam dose per monitor unit calculations

    SciTech Connect

    Hsi, Wen C.; Schreuder, Andries N.; Moyers, Michael F.; Allgower, Chris E.; Farr, Jonathan B.; Mascia, Anthony E.

    2009-02-15

    Calculations of dose per monitor unit (D/MU) are required in addition to measurements to increase patient safety in the clinical practice of proton radiotherapy. As in conventional photon and electron therapy, the D/MU depends on several factors. This study focused on obtaining range and modulation dependence factors used in D/MU calculations for the double scattered proton beam line at the Midwest Proton Radiotherapy Institute. Three dependencies on range and one dependency on modulation were found. A carefully selected set of measurements was performed to discern these individual dependencies. Dependencies on range were due to: (1) the stopping power of the protons passing through the monitor chamber; (2) the reduction of proton fluence due to nuclear interactions within the patient; and (3) the variation of proton fluence passing through the monitor chamber due to different source-to-axis distances (SADs) for different beam ranges. Different SADs are produced by reconfigurations of beamline elements to provide different field sizes and ranges. The SAD effect on the D/MU varies smoothly as the beam range is varied, except at the beam range for which the first scatterers are exchanged and relocated to accommodate low and high beam ranges. A geometry factor was devised to model the SAD variation effect on the D/MU. The measured D/MU variation as a function of range can be predicted within 1% using the three modeled dependencies on range. Investigation of modulated beams showed that an analytical formula can predict the D/MU dependency as a function of modulation to within 1.5%. Special attention must be applied when measuring the D/MU dependence on modulation to avoid interplay between range and SAD effects.

  19. Two Week Oral Dose Range-Finding Toxicity Study of WR242511 in Rats

    DTIC Science & Technology

    1993-07-08

    Test Article: WR242511 Tartrate Contract No.: DAMD17-92-C-2001 Study Director Barry S. Levine, D.Sc, D.A.B.T. In-Life Phase Completed On July 8...Page TWO WEEK ORAL DOSE RANGE-FINDING TOXICITY STUDY OF WR242511 IN RATS Bfifir TRL Chemical No.: Sponsor: Sponsor Representative: Testing ...7 2. INTRODUCTION 7 3. MATERIALS AND METHODS 7 3.1 Test Article 7 3.2 Animals 8 3.3 Experimental Design 8 3.4

  20. Preclinical Dose Ranging Studies of a Novel Dry Powder Norovirus Vaccine Formulation

    PubMed Central

    Springer, Michael J.; Ni, Yawei; Finger-Baker, Isaac; Ball, Jordan P.; Hahn, Jessica; DiMarco, Ashley V.; Kobs, Dean; Horne, Bobbi; Talton, James D.; Cobb, Ronald R.

    2016-01-01

    Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVac™) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose dependant manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVac™ formulation, a total antigen dose of ≥15 µg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLP based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimilatory adjuvant and provides a basis for the development of a GelVac™ bivalent GI/GII.4 norovirus VLP vaccine. PMID:26873053

  1. A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single doses of betaxolol.

    PubMed Central

    Irvine, N A; Lipworth, B J; McDevitt, D G

    1990-01-01

    1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20 mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was assessed by reductions in exercise heart rate. Betaxolol produced dose-related reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20, 116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was assessed by attenuation of finger tremor and cardiovascular responses to graded infusions of i.v. isoprenaline. Dose-response curves were constructed and the doses required to increase heart rate by 25 beats min-1, finger tremor by 200%, calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10 mm Hg, after each treatment were calculated. These were then compared with placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor showed significant attenuation by all doses of betaxolol (compared with PL): B10 1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55 +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40 6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1975196

  2. Radiation dose response estimation with emphasis on low dose range using restricted cubic splines: application to all solid cancer mortality data, 1950-2003, in atomic bomb survivors.

    PubMed

    Nakashima, Eiji

    2015-07-01

    Using the all solid cancer mortality data set of the Life Span Study (LSS) cohort from 1950 to 2003 (LSS Report 14) data among atomic bomb survivors, excess relative risk (ERR) statistical analyses were performed using the second degree polynomial and the threshold and restricted cubic spline (RCS) dose response models. For the RCS models with 3 to 7 knots of equally spaced percentiles with margins in the dose range greater than 50 mGy, the dose response was assumed to be linear at less than 70 to 90 mGy. Due to the skewed dose distribution of atomic bomb survivors, the current knot system for the RCS analysis results in a detailed depiction of the dose response as less than approximately 0.5 Gy. The 6 knot RCS models for the all-solid cancer mortality dose response of the whole dose or less than 2 Gy were selected with the AIC model selection criterion and fit significantly better (p < 0.05) than the linear (L) model. The usual RCS includes the L-global model but not the quadratic (Q) nor linear-quadratic (LQ) global models. The authors extended the RCS to include L or LQ global models by putting L or LQ constraints on the cubic spline in the lower and upper tails, and the best RCS model selected with AIC criterion was the usual RCS with L-constraints in both the lower and upper tails. The selected RCS had a linear dose-response model in the lower dose range (i.e., < 0.2-0.3 Gy) and was compatible with the linear no-threshold (LNT) model in this dose range. The proposed method is also useful in describing the dose response of a specific cancer or non-cancer disease incidence/mortality.

  3. Dose Range-Finding Developmental Toxicity Study of WR242511 in Rats

    DTIC Science & Technology

    1994-05-06

    period. Rough coat was also observed in three females during GDI3 -15. The 4 mg base/kg/day dose was considered near or at the maternal no observable...the dosing period (i.e. GDI3 -15), and was not apparent in the lower dose levels. 4.2 Maternal Body Weights The summaries of maternal body weights

  4. Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.

    PubMed

    Dorman, Susan E; Savic, Radojka M; Goldberg, Stefan; Stout, Jason E; Schluger, Neil; Muzanyi, Grace; Johnson, John L; Nahid, Payam; Hecker, Emily J; Heilig, Charles M; Bozeman, Lorna; Feng, Pei-Jean I; Moro, Ruth N; MacKenzie, William; Dooley, Kelly E; Nuermberger, Eric L; Vernon, Andrew; Weiner, Marc

    2015-02-01

    Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

  5. Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film.

    PubMed

    Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

    2016-01-01

    Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were -32.336 and -33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range.

  6. Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film

    PubMed Central

    Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

    2016-01-01

    Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were −32.336 and −33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range. PMID:28144120

  7. Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements

    PubMed Central

    Bentefour, El H.; Tang, Shikui; Cascio, Ethan W.; Testa, Mauro; Samuel, Deepak; Prieels, Damien; Gottschalk, Bernard; Lu, Hsiao-Ming

    2015-01-01

    Purpose: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. Methods: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. Results: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. Conclusions: Time-resolved dose

  8. Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements

    SciTech Connect

    Bentefour, El H. Prieels, Damien; Tang, Shikui; Cascio, Ethan W.; Testa, Mauro; Lu, Hsiao-Ming; Samuel, Deepak; Gottschalk, Bernard

    2015-04-15

    Purpose: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. Methods: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. Results: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. Conclusions: Time-resolved dose

  9. Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066).

    PubMed

    Hendrix, Craig W; Andrade, Adriana; Bumpus, Namandjé N; Kashuba, Angela D; Marzinke, Mark A; Moore, Ayana; Anderson, Peter L; Bushman, Lane R; Fuchs, Edward J; Wiggins, Ilene; Radebaugh, Christine; Prince, Heather A; Bakshi, Rahul P; Wang, Ruili; Richardson, Paul; Shieh, Eugenie; McKinstry, Laura; Li, Xin; Donnell, Deborah; Elharrar, Vanessa; Mayer, Kenneth H; Patterson, Kristine B

    2016-01-01

    Oral preexposure prophylaxis (PrEP) trials report disparate efficacy attributed to variable adherence. HPTN 066 was conducted to establish objective, quantitative benchmarks for discrete, regular levels of adherence using directly observed dosing of tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC). Healthy, HIV-uninfected men and women were randomized to one of four oral regimens of fixed-dose TDF 300 mg/FTC 200 mg tablet for 5 weeks with all doses observed: one tablet weekly (one/week), one tablet twice weekly (two/week), two tablets twice weekly (four/week), or one tablet daily (seven/week). Trough serum TFV and FTC, peripheral blood mononuclear cell (PBMC), and CD4(+) TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) concentrations were determined throughout dosing and 2 weeks after the last dose. Rectosigmoidal, semen, and cervicovaginal samples were collected for drug assessment at end of dosing and 2 weeks later in a subset of participants. The 49 enrolled participants tolerated the regimens well. All regimens achieved steady-state concentrations by the second dose for serum TFV/FTC and by 7 days for PBMC TFV-DP/FTC-TP. Steady-state median TFV-DP predose concentrations demonstrated dose proportionality: one/week 1.6 fmol/10(6) PBMCs, two/week 9.1, four/week 18.8, seven/week, 36.3. Further, TFV-DP was consistently quantifiable 2 weeks after the last dose for the ≥4/week regimens. Adherence benchmarks were identified using receiver operating characteristic curves, which had areas under the curve ≥0.93 for all analytes in serum and PBMCs. Intersubject and intrasubject coefficients of variation (%CV) ranged from 33% to 63% and 14% to 34%, respectively, for all analytes in serum and PBMCs. Steady-state PBMC TFV-DP was established earlier and at lower concentrations than predicted and was the only analyte demonstrating predose concentration dose proportionality. Steady-state daily dosing serum TFV and PBMC TFV-DP was consistent with

  10. Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066)

    PubMed Central

    Andrade, Adriana; Bumpus, Namandjé N.; Kashuba, Angela D.; Marzinke, Mark A.; Moore, Ayana; Anderson, Peter L.; Bushman, Lane R.; Fuchs, Edward J.; Wiggins, Ilene; Radebaugh, Christine; Prince, Heather A.; Bakshi, Rahul P.; Wang, Ruili; Richardson, Paul; Shieh, Eugenie; McKinstry, Laura; Li, Xin; Donnell, Deborah; Elharrar, Vanessa; Mayer, Kenneth H.; Patterson, Kristine B.

    2016-01-01

    Abstract Oral preexposure prophylaxis (PrEP) trials report disparate efficacy attributed to variable adherence. HPTN 066 was conducted to establish objective, quantitative benchmarks for discrete, regular levels of adherence using directly observed dosing of tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC). Healthy, HIV-uninfected men and women were randomized to one of four oral regimens of fixed-dose TDF 300 mg/FTC 200 mg tablet for 5 weeks with all doses observed: one tablet weekly (one/week), one tablet twice weekly (two/week), two tablets twice weekly (four/week), or one tablet daily (seven/week). Trough serum TFV and FTC, peripheral blood mononuclear cell (PBMC), and CD4+ TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) concentrations were determined throughout dosing and 2 weeks after the last dose. Rectosigmoidal, semen, and cervicovaginal samples were collected for drug assessment at end of dosing and 2 weeks later in a subset of participants. The 49 enrolled participants tolerated the regimens well. All regimens achieved steady-state concentrations by the second dose for serum TFV/FTC and by 7 days for PBMC TFV-DP/FTC-TP. Steady-state median TFV-DP predose concentrations demonstrated dose proportionality: one/week 1.6 fmol/106 PBMCs, two/week 9.1, four/week 18.8, seven/week, 36.3. Further, TFV-DP was consistently quantifiable 2 weeks after the last dose for the ≥4/week regimens. Adherence benchmarks were identified using receiver operating characteristic curves, which had areas under the curve ≥0.93 for all analytes in serum and PBMCs. Intersubject and intrasubject coefficients of variation (%CV) ranged from 33% to 63% and 14% to 34%, respectively, for all analytes in serum and PBMCs. Steady-state PBMC TFV-DP was established earlier and at lower concentrations than predicted and was the only analyte demonstrating predose concentration dose proportionality. Steady-state daily dosing serum TFV and PBMC TFV-DP was consistent with

  11. The basic study of a bi-material range compensator for improving dose uniformity for proton therapy.

    PubMed

    Takada, Yoshihisa; Himukai, Takeshi; Takizawa, Kenji; Terashita, Yohsuke; Kamimura, Satoshi; Matsuda, Hiroshi; Hotta, Kenji; Kohno, Ryosuke; Komori, Masataka; Kanai, Tatsuaki

    2008-10-07

    A range compensator (abbreviated as a RC hereafter) is used to form a conformal dose distribution for heavy-charged-particle therapy. However, it induces distortion of the dose distribution. The induced inhomogeneity may result in a calibration error of a monitor unit (MU) assigned to a transmission ionization chamber. By using a bi-material RC made from a low-Z material and a high-Z material instead of the regular RC, the dose inhomogeneity has been obviously reduced by equalizing the lateral dose distributions formed by pencil beams traversing elements of the RC with different base thicknesses at the same water-equivalent depth. We designed and manufactured a 4 x 4 matrix-shaped single-material RC and a bi-material RC with the same range losses at corresponding elements of the RCs. The bi-material RC is made from chemical wood (the main chemical component is an ABS resin) as a low-Z material and from brass as a high-Z material. Sixteen segments of the RC are designed so that the range-loss differences of the adjacent segments of the RC range from 0 to 50 mm in steps of 5 mm. We measured dose distributions in water formed by a 160 MeV proton beam traversing the single-material RC or the bi-material RC, using the HIMAC biology beam port. Large dips and bumps were observed in the dose distribution formed by the use of the single-material RC; the dose uniformity has been significantly improved in the target region by the use of the bi-material RC. The improvement has been obtained at the expense of blurring lateral penumbra. For clinical application of this method to a patient with large density inhomogeneity, a simple modification method of the original calculation model has been given.

  12. SU-E-T-324: The Influence of Patient Positioning Uncertainties in Proton Radiotherapy On Proton Range and Dose Distributions

    SciTech Connect

    Liebl, J; Paganetti, H; Winey, B

    2014-06-01

    Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: 38 clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50% and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs) and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: We identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 mm and 5.8 mm for the 90%-dose falloff position respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. TCP decreases larger than 10% (absolute) were seen for less than 2.2% of the target volumes or non-existent. EUD changes were up to 178% for OARs and 35% for target volumes. Conclusion: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the human brain and target and OAR dosimetry were studied. Observed range uncertainties were correlated with HIs. The clinical practice of using multiple compensator

  13. Personal dose equivalent conversion coefficients for neutron fluence over the energy range of 20-250 MeV.

    PubMed

    Olsher, R H; McLean, T D; Justus, A L; Devine, R T; Gadd, M S

    2010-03-01

    Monte Carlo simulations were performed to extend existing neutron personal dose equivalent fluence-to-dose conversion coefficients to an energy of 250 MeV. Presently, conversion coefficients, H(p,slab)(10,alpha)/Phi, are given by ICRP-74 and ICRU-57 for a range of angles of radiation incidence (alpha = 0, 15, 30, 45, 60 and 75 degrees ) in the energy range from thermal to 20 MeV. Standard practice has been to base operational dose quantity calculations <20 MeV on the kerma approximation, which assumes that charged particle secondaries are locally deposited, or at least that charged particle equilibrium exists within the tally cell volume. However, with increasing neutron energy the kerma approximation may no longer be valid for some energetic secondaries such as protons. The Los Alamos Monte Carlo radiation transport code MCNPX was used for all absorbed dose calculations. Transport models and collision-based energy deposition tallies were used for neutron energies >20 MeV. Both light and heavy ions (HIs) (carbon, nitrogen and oxygen recoil nuclei) were transported down to a lower energy limit (1 keV for light ions and 5 MeV for HIs). Track energy below the limit was assumed to be locally deposited. For neutron tracks <20 MeV, kerma factors were used to obtain absorbed dose. Results are presented for a discrete set of angles of incidence on an ICRU tissue slab phantom.

  14. Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

    PubMed

    Solish, Nowell; Rivers, Jason K; Humphrey, Shannon; Muhn, Channy; Somogyi, Chris; Lei, Xiaofang; Bhogal, Meetu; Caulkins, Carrie

    2016-03-01

    Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

  15. Four Week Oral Dose Range-Finding Study of WR242511 in Dogs

    DTIC Science & Technology

    1994-03-09

    Laboratory, Model No. 282). The assay was performed within one-hour of sample collection. The specimens were kept on wet ice prior to analysis...this protein, which is synthesized by hepatocytes, is indicative of an inflammatory response, i.e. an acute phase reaction . Dose-dependent anemia, as...apparent decreases in the A/G ratio, and increases in serum haptoglobin levels, indicative of an acute phase reaction . In the lung, WR242511 resulted in

  16. Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

    PubMed

    Inaniwa, Taku; Kohno, Toshiyuki; Tomitani, Takehiro; Urakabe, Eriko; Sato, Shinji; Kanazawa, Mitsutaka; Kanai, Tatsuaki

    2006-09-07

    In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an

  17. Accuracy and Radiation Dose Reduction of Limited-Range CT in the Evaluation of Acute Appendicitis in Pediatric Patients.

    PubMed

    Jin, Michael; Sanchez, Thomas R; Lamba, Ramit; Fananapazir, Ghaneh; Corwin, Michael T

    2017-09-01

    The purpose of this article is to determine the accuracy and radiation dose reduction of limited-range CT prescribed from the top of L2 to the top of the pubic symphysis in children with suspected acute appendicitis. We performed a retrospective study of 210 consecutive pediatric patients from December 11, 2012, through December 11, 2014, who underwent abdominopelvic CT for suspected acute appendicitis. Two radiologists independently reviewed the theoretic limited scans from the superior L2 vertebral body to the top of the pubic symphysis, to assess for visualization of the appendix, acute appendicitis, alternative diagnoses, and incidental findings. Separately, the same parameters were assessed on the full scan by the same two reviewers. Whole-body effective doses were determined for the full- and limited-range scans and were compared using the paired t test. The appendix or entire cecum was visualized on the limited scan in all cases, and no cases of acute appendicitis were missed on the simulated limited scan compared with the full scan. Two alternative diagnoses were missed with the limited scan: one case of hydronephrosis and one of acute acalculous cholecystitis. The mean effective dose for the original scan was 5.6 mSv and that for the simulated limited scan was 3.0 mSv, resulting in a dose reduction of 46.4% (p < 0.001). A limited-range CT examination performed from the top of L2 to the top of the pubic symphysis is as accurate as a full-range abdominopelvic CT in evaluating pediatric patients with suspected appendicitis and reduces the dose by approximately 46%.

  18. Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol.

    PubMed

    Steiner, T J; Lange, R; Voelker, M

    2003-02-01

    Most people with episodic tension-type headache (TTH) treat themselves with over-the-counter analgesics. In the absence of clear evidence of dose-related efficacy of the two most commonly used analgesics, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), this study compared two doses of each with placebo. In a double-blind, double-dummy, randomized parallel-groups comparative trial, 638 consenting subjects aged 16-65 years with episodic TTH (but not migraine) by IHS criteria were recruited from the UK general population by advertisement. They treated one episode of moderate or severe TTH with a single dose of 500 or 1000 mg aspirin, 500 or 1000 mg paracetamol or placebo. The primary objective was to compare aspirin 1000 mg with placebo, and the primary end-point was subjective pain relief (total or worthwhile) 2 h after treatment ('response'). Additionally, pain intensity on a 100-mm visual analogue scale and functional impairment were monitored regularly for 4 h and at 24 h, although rescue medication was allowed after 2 h. The analysis was of the intention-to-treat population of 542 who took treatment (all providing outcome data). Treatment groups were matched at baseline. Aspirin 1000 mg (75.7% response rate; P = 0.0009) and to a lesser extent aspirin 500 mg (70.3%; P = 0.011) and paracetamol 1000 mg (71.2%; P = 0.007), but not paracetamol 500 mg (63.8%; P = 0.104), were statistically more effective than placebo despite a high placebo-response rate (54.5%). Outcome was not affected by headache intensity at baseline. Secondary end-points including functional recovery (by median times of 4.0-13.5 h) were consistent with these findings, although a minority of subjects recorded long-duration functional impairment (37-54 h). Adverse events reported by 13.4-18.9% of subjects were mild or moderate, and transient. No safety concerns arose.

  19. Blonanserin extensively occupies rat dopamine D3 receptors at antipsychotic dose range.

    PubMed

    Baba, Satoko; Enomoto, Takeshi; Horisawa, Tomoko; Hashimoto, Takashi; Ono, Michiko

    2015-03-01

    Antagonism of the dopamine D3 receptor has been hypothesized to be beneficial for schizophrenia cognitive deficits, negative symptoms and extrapyramidal symptoms. However, recent animal and human studies have shown that most antipsychotics do not occupy D3 receptors in vivo, despite their considerable binding affinity for this receptor in vitro. In the present study, we investigated the D3 receptor binding of blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptors antagonist, in vitro and in vivo. Blonanserin showed the most potent binding affinity for human D3 receptors among the tested atypical antipsychotics (risperidone, olanzapine and aripiprazole). Our GTPγS-binding assay demonstrated that blonanserin acts as a potent full antagonist for human D3 receptors. All test-drugs exhibited antipsychotic-like efficacy in methamphetamine-induced hyperactivity in rats. Treatment with blonanserin at its effective dose blocked the binding of [(3)H]-(+)-PHNO, a D2/D3 receptor radiotracer, both in the D2 receptor-rich region (striatum) and the D3 receptor-rich region (cerebellum lobes 9 and 10). On the other hand, the occupancies of other test-drugs for D3 receptors were relatively low. In conclusion, we have shown that blonanserin, but not other tested antipsychotics, extensively occupies D3 receptors in vivo in rats. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  20. A radiochromic folm dosimeter for gamma radiation in the absorbed-dose range 0.1-10 kGy

    NASA Astrophysics Data System (ADS)

    Khan, Hasan M.; Farahani, Mahnaz; William L., McLaughlin

    A commercially available leuco-dye film (FWT-63-02), having a thickness of 0.55 mm, has been investigated spectrophotometrically for its characteristics as a radiochromic dosimeter and for its potential use in food-irradiation applications. The γ-ray irradiation of the nearly colorless, transparent film induces blue color with an absorption maximum at 600 nm. The increase in absorbance at 600 nm per unit thickness of film (Δ A mm -1) is linear with dose in the dose range up to 8 kGy, with a slope of 0.91 mm -1·kGy -1. After a modest additional increase during the first day following irradiation, the radiation-induced color is stable when stored at room temperature at least for 5 weeks. The response slope is 16% higher when stored at 60°C, however, after the initial 1-day increase it is stable for several weeks when stored at that temperature. The response of the dosimeter is independent of dose rate in the range 0.5-170 Gy min -1.

  1. SU-E-J-140: Simulation Study Using Thermoacoustics to Image Proton Dose and Range in Water and Skull Phantom

    SciTech Connect

    Stantz, K; Moskvin, V

    2015-06-15

    Purpose: In this study, thermoacoustic pressure signals generated from a proton beam were simulated in water and currently within a skull phantom to investigate the sensitivity of radioacoustic CT imaging in the brain. Methods: Thermoacoustically generated pressure signals from a pulse pencil proton beam (12, 15, 20, and 27cm range) were simulated in water. These simulated pressure signal are detected using a (71) transducer array placed along the surface of a cylinder (30cm × 40cm) and rotated over 2π (in 2 degree increments), where the normal vector to the surface of each transducer intersects the isocenter of the scanner. Currently, a software skull phantom is positioned at isocenter, where the scattering, absorption and speed of dispersion of the thermoacoustic signal through a three layer cortical-trabecular-cortical structure is being simulated. Based on data obtained from the literature, the effects of acoustic attenuation and speed-of-sound (dispersion) will be applied within the 3D FBP algorithm to obtain dosimetric images. Results: Based on hydrophone detector specifications, a 0.5MHz bandwidth and 50dB re 1μPa per Hz^1/2, a 1.6cGy sensitivity at the Bragg peak was demonstrated while maintaining a 1.0 mm (FWHM) range resolution along the central axis of the beam. Utilizing this same information, the integral dose within the Bragg peak and distal edge compared to MC had a 2% (statistical) and 5% voxel-based RMS at this same dose sensitivity. We plan to present preliminary data determining the range sensitivity for a head phantom for this scanner design and the feasibility of imaging the proton dose in patients with a brain tumor undergoing therapy. Conclusion: RACT scanner provides 3D dosimetric images with 1.6cGy (Bragg peak) sensitivity with 1mm range sensitivity. Simulations will be performed to determine feasibility to treat brain cancer patients.

  2. Computerized Dose Range Checking Using Hard and Soft Stop Alerts Reduces Prescribing Errors in a Pediatric Intensive Care Unit.

    PubMed

    Balasuriya, Lilanthi; Vyles, David; Bakerman, Paul; Holton, Vanessa; Vaidya, Vinay; Garcia-Filion, Pamela; Westdorp, Joan; Sanchez, Christine; Kurz, Rhonda

    2017-09-01

    An enhanced dose range checking (DRC) system was developed to evaluate prescription error rates in the pediatric intensive care unit and the pediatric cardiovascular intensive care unit. An enhanced DRC system incorporating "soft" and "hard" alerts was designed and implemented. Practitioner responses to alerts for patients admitted to the pediatric intensive care unit and the pediatric cardiovascular intensive care unit were retrospectively reviewed. Alert rates increased from 0.3% to 3.4% after "go-live" (P < 0.001). Before go-live, all alerts were soft alerts. In the period after go-live, 68% of alerts were soft alerts and 32% were hard alerts. Before go-live, providers reduced doses only 1 time for every 10 dose alerts. After implementation of the enhanced computerized physician order entry system, the practitioners responded to soft alerts by reducing doses to more appropriate levels in 24.7% of orders (70/283), compared with 10% (3/30) before go-live (P = 0.0701). The practitioners deleted orders in 9.5% of cases (27/283) after implementation of the enhanced DRC system, as compared with no cancelled orders before go-live (P = 0.0774). Medication orders that triggered a soft alert were submitted unmodified in 65.7% (186/283) as compared with 90% (27/30) of orders before go-live (P = 0.0067). After go-live, 28.7% of hard alerts resulted in a reduced dose, 64% resulted in a cancelled order, and 7.4% were submitted as written. Before go-live, alerts were often clinically irrelevant. After go-live, there was a statistically significant decrease in orders that were submitted unmodified and an increase in the number of orders that were reduced or cancelled.

  3. Characterizing the time-course of antihypertensive activity and optimal dose range of fimasartan via mechanism-based population modeling.

    PubMed

    Bulitta, Jürgen B; Paik, Soo Heui; Chi, Yong Ha; Kim, Tae Hwan; Shin, Soyoung; Landersdorfer, Cornelia B; Jiao, Yuanyuan; Yadav, Rajbharan; Shin, Beom Soo

    2017-09-30

    Fimasartan is a novel angiotensin II receptor blocker. Our aims were to characterize the time-course of the antihypertensive activity of fimasartan via a new population pharmacokinetic/pharmacodynamic model and to define its optimal dose range. We simultaneously modelled all fimasartan plasma concentrations and 24-h ambulatory blood pressure monitoring (ABPM) data from 39 patients with essential hypertension and 56 healthy volunteers. Patients received placebo, 20, 60, or 180mg fimasartan every 24h for 28days and healthy volunteers received placebo or 20 to 480mg as a single oral dose or as seven doses every 24h. External validation was performed using data on 560 patients from four phase II or III studies. One turnover model each was used to describe diastolic and systolic blood pressure. The input rates into these compartments followed a circadian rhythm and were inhibited by fimasartan. The average predicted (observed) diastolic blood pressure over 24-h in patients decreased by 10.1±7.5 (12.6±9.2; mean±SD)mmHg for 20mg, 14.2±7.0 (15.1±9.3) mmHg for 60mg, and 15.9±6.8 (11.5±9.9)mmHg for 180mg daily relative to placebo. The model explained the saturation of antihypertensive activity by counter-regulation at high fimasartan concentrations. Drug effect was maximal at approximately 23ng/mL fimasartan for diastolic and 12ng/mL for systolic blood pressure. The proposed mechanism-based population model characterized the circadian rhythm of ABPM data and the antihypertensive effect of fimasartan. After internal and external model validation, 30 to 60mg oral fimasartan given once daily was predicted as optimal dose range. Copyright © 2017. Published by Elsevier B.V.

  4. 12 CFR 3.20 - Change in circumstances.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Change in circumstances. 3.20 Section 3.20 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS; ISSUANCE OF DIRECTIVES Issuance of a Directive § 3.20 Change in circumstances. Upon a change...

  5. 12 CFR 3.20 - Change in circumstances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Change in circumstances. 3.20 Section 3.20 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS; ISSUANCE OF DIRECTIVES Issuance of a Directive § 3.20 Change in circumstances. Upon a change...

  6. A dose-ranging study of tiotropium delivered via Respimat Soft Mist Inhaler or HandiHaler in COPD patients.

    PubMed

    Caillaud, Denis; Le Merre, Charles; Martinat, Yan; Aguilaniu, Bernard; Pavia, Demetri

    2007-01-01

    This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study. COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 microg, 2.5 microg, 5 microg, 10 microg, or 20 microg Respimat SMI (a novel, propellant-free device); tiotropium 18 microg HandiHaler; placebo Respimat; or placebo HandiHaler for 3 weeks. The primary endpoint was trough FEV1 on Day 21. Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics. In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo. Tiotropium 5 microg Respimat, 20 microg Respimat, and tiotropium 18 microg HandiHaler were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV1 was 150 mL (both Respimat doses) versus 20 mL (placebo Respimat); p < 0.05; and 230 mL (HandiHaler) versus -90 mL (placebo HandiHaler); p < or = 0.001). The urinary excretion (up to 2 hours post-dose) of tiotropium 5-10 microg Respimat was comparable with tiotropium 18 microg HandiHaler; the overall incidence of adverse events was comparable across treatment groups. Tiotropium 5 and 10 microg Respimat improve lung function in COPD patients and appear to be comparable with tiotropium 18 microg HandiHaler.

  7. Otilonium bromide in irritable bowel syndrome: A dose-ranging randomized double-blind placebo-controlled trial

    PubMed Central

    Chmielewska-Wilkoń, Danuta; Reggiardo, Giorgio; Egan, Colin Gerard

    2014-01-01

    AIM: To examine the efficacy and safety of otilonium bromide (OB) in treatment-sensitive functional irritable bowel syndrome (IBS) clinical parameters. METHODS: Ninety-three patients (44.8 ± 12.6 years, 69% female) with IBS symptoms complying with Rome II criteria participated in this double-blind, placebo-controlled, randomised, dose-ranging phase I/II study. Patients were administered OB 20 mg (n = 24), 40mg (n = 23) and 80 mg (n = 23) tid or placebo (n = 23) in 4 parallel groups for 4 wk. Primary efficacy variables included abdominal discomfort, intestinal habits, number of daily evacuations and stool consistency. Secondary efficacy measures included return to regular intestinal habits and global discomfort. Safety was also assessed. RESULTS: Baseline clinical characteristics were similar among the 4 groups. Although individual parameters such as intensity and frequency of abdominal discomfort, bloating or pain were reduced by OB over the 4 wk, no significant differences were observed between groups. Similarly, no difference was observed between OB treatment or placebo for mucus in stool and incomplete or difficulty of evacuation. However, evacuation frequency was significantly reduced after 4 wk by 80 mg OB compared to placebo (-8.36% for placebo vs -41.9% for 80 mg OB, P < 0.01). While 21.7% of patients in the placebo group experienced regular intestinal habits after 4 wk, this improvement was greater for patients treated with 40 mg OB (P < 0.01 vs placebo). Furthermore, a dose-dependent reduction in frequency of diarrhoea (χ2-test for trend = 11.5, P < 0.001) and an increase in normal stool frequency was observed. Combining individual variables into a global discomfort index revealed significant improvement among increasing OB doses, favouring 40 mg (P = 0.013) and 80mg OB (P = 0.001) over placebo. No difference was observed between frequency of adverse events for placebo vs OB. CONCLUSION: This dose-ranging study demonstrates that OB at 40 and 80 mg can

  8. Otilonium bromide in irritable bowel syndrome: a dose-ranging randomized double-blind placebo-controlled trial.

    PubMed

    Chmielewska-Wilkoń, Danuta; Reggiardo, Giorgio; Egan, Colin Gerard

    2014-09-14

    To examine the efficacy and safety of otilonium bromide (OB) in treatment-sensitive functional irritable bowel syndrome (IBS) clinical parameters. Ninety-three patients (44.8 ± 12.6 years, 69% female) with IBS symptoms complying with Rome II criteria participated in this double-blind, placebo-controlled, randomised, dose-ranging phase I/II study. Patients were administered OB 20 mg (n = 24), 40 mg (n = 23) and 80 mg (n = 23) tid or placebo (n = 23) in 4 parallel groups for 4 wk. Primary efficacy variables included abdominal discomfort, intestinal habits, number of daily evacuations and stool consistency. Secondary efficacy measures included return to regular intestinal habits and global discomfort. Safety was also assessed. Baseline clinical characteristics were similar among the 4 groups. Although individual parameters such as intensity and frequency of abdominal discomfort, bloating or pain were reduced by OB over the 4 wk, no significant differences were observed between groups. Similarly, no difference was observed between OB treatment or placebo for mucus in stool and incomplete or difficulty of evacuation. However, evacuation frequency was significantly reduced after 4 wk by 80 mg OB compared to placebo (-8.36% for placebo vs -41.9% for 80 mg OB, P < 0.01). While 21.7% of patients in the placebo group experienced regular intestinal habits after 4 wk, this improvement was greater for patients treated with 40 mg OB (P < 0.01 vs placebo). Furthermore, a dose-dependent reduction in frequency of diarrhoea (χ(2)-test for trend = 11.5, P < 0.001) and an increase in normal stool frequency was observed. Combining individual variables into a global discomfort index revealed significant improvement among increasing OB doses, favouring 40 mg (P = 0.013) and 80 mg OB (P = 0.001) over placebo. No difference was observed between frequency of adverse events for placebo vs OB. This dose-ranging study demonstrates that OB at 40 and 80 mg can improve individual and global

  9. Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

    PubMed

    Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len

    2014-02-01

    Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.

  10. Upgrades of DARWIN, a dose and spectrum monitoring system applicable to various types of radiation over wide energy ranges

    NASA Astrophysics Data System (ADS)

    Sato, Tatsuhiko; Satoh, Daiki; Endo, Akira; Shigyo, Nobuhiro; Watanabe, Fusao; Sakurai, Hiroki; Arai, Yoichi

    2011-05-01

    A dose and spectrum monitoring system applicable to neutrons, photons and muons over wide ranges of energy, designated as DARWIN, has been developed for radiological protection in high-energy accelerator facilities. DARWIN consists of a phoswitch-type scintillation detector, a data-acquisition (DAQ) module for digital waveform analysis, and a personal computer equipped with a graphical-user-interface (GUI) program for controlling the system. The system was recently upgraded by introducing an original DAQ module based on a field programmable gate array, FPGA, and also by adding a function for estimating neutron and photon spectra based on an unfolding technique without requiring any specific scientific background of the user. The performance of the upgraded DARWIN was examined in various radiation fields, including an operational field in J-PARC. The experiments revealed that the dose rates and spectra measured by the upgraded DARWIN are quite reasonable, even in radiation fields with peak structures in terms of both spectrum and time variation. These results clearly demonstrate the usefulness of DARWIN for improving radiation safety in high-energy accelerator facilities.

  11. A dose-ranging study of the pharmacokinetics of hydroxy-chloroquine following intravenous administration to healthy volunteers.

    PubMed

    Tett, S E; Cutler, D J; Day, R O; Brown, K F

    1988-09-01

    1. The pharmacokinetics of hydroxychloroquine were studied in five healthy volunteers following an intravenous infusion of 155 mg (2.47 +/- 0.25 mg kg-1) racemic hydroxychloroquine. Four of these volunteers also received a further 310 mg (4.92 +/- 0.45 mg kg-1) infusion of hydroxychloroquine and evidence of nonlinearities in the pharmacokinetics of hydroxychloroquine were sought. 2. No nonlinear elimination or distribution processes appeared to be operating at the doses of hydroxychloroquine used in this study, supporting the hypothesis that in the therapeutic dosing range the pharmacokinetics of hydroxychloroquine are linear. 3. Half-life and mean residence time were long (around 40 days) and large volumes of distribution were calculated (5,522 l from blood, 44,257 l from plasma). Sequestration into the tissues is an important feature of the disposition of hydroxychloroquine. The persistence of hydroxychloroquine in the body is due primarily to this extensive tissue distribution, rather than to low clearance (667 ml min-1 based on plasma data, 96 ml min-1 based on blood data). 4. Plasma data were more variable than blood data. Blood to plasma concentration ratios were not constant (mean +/- s.d.: 7.2 +/- 4.2). The data indicate that it is preferable to measure whole blood concentrations of hydroxychloroquine, rather than plasma concentrations, in pharmacokinetic studies. 5. The pharmacokinetics of hydroxychloroquine are similar to those of chloroquine.

  12. Construction of a cytogenetic dose-response curve for low-dose range gamma-irradiation in human peripheral blood lymphocytes using three-color FISH.

    PubMed

    Suto, Yumiko; Akiyama, Miho; Noda, Takashi; Hirai, Momoki

    2015-12-01

    In order to estimate biological doses after low-dose ionizing radiation exposure, fluorescence in situ hybridization (FISH) using three differentially colored chromosome painting probes was employed to detect exchange-type chromosome aberrations. A reference dose response curve was constructed using blood samples from a female donor whose lymphocytes consistently exhibited a low frequency of cells at the second mitosis under routine culture conditions. Aberration yields were studied for a total of about 155 thousand metaphases obtained from seven dose-points of gamma irradiations (0, 50, 100, 150, 200, 250 and 300mGy). In situ hybridization was performed using commercially available painting probes for chromosomes 1, 2 and 4. With the aid of an automated image-capturing method, exchange-type aberrations involving painted chromosomes were detected with considerable accuracy and speed. The results on the exchange-type aberrations (dicentrics plus translocations) at the seven dose-points showed a good fit to the linear-quadratic model (y=0.0023+0.0015x+0.0819x(2), P=0.83). A blind test proved the reproducibility of the reference dose-response relationship. In the control experiments using blood samples from another donor, the estimated doses calculated on the basis of the present reference curve were proved to be in good agreement with the actual physical doses applied. The present dose-response curve may serve as a means to assess the individual differences in cytogenetical radio-sensitivities.

  13. 12 CFR 3.20 - Change in circumstances.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Change in circumstances. 3.20 Section 3.20 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS... the plan to achieve the bank's applicable minimum capital ratios. The Office also may take such...

  14. 12 CFR 3.20 - Change in circumstances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Change in circumstances. 3.20 Section 3.20 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS... the plan to achieve the bank's applicable minimum capital ratios. The Office also may take such...

  15. First international comparison of primary absorbed dose to water standards in the medium-energy X-ray range

    NASA Astrophysics Data System (ADS)

    Büermann, Ludwig; Guerra, Antonio Stefano; Pimpinella, Maria; Pinto, Massimo; de Pooter, Jacco; de Prez, Leon; Jansen, Bartel; Denoziere, Marc; Rapp, Benjamin

    2016-01-01

    This report presents the results of the first international comparison of primary measurement standards of absorbed dose to water for the medium-energy X-ray range. Three of the participants (VSL, PTB, LNE-LNHB) used their existing water calorimeter based standards and one participant (ENEA) recently developed a new standard based on a water-graphite calorimeter. The participants calibrated three transfer chambers of the same type in terms of absorbed dose to water (NDw) and in addition in terms of air kerma (NK) using the CCRI radiation qualities in the range 100 kV to 250 kV. The additional NK values were intended to be used for a physical analysis of the ratios NDw/NK. All participants had previously participated in the BIPM.RI(I)-K3 key comparison of air kerma standards. Ratios of pairs of NMI's NK results of the current comparison were found to be consistent with the corresponding key comparison results within the expanded uncertainties of 0.6 % - 1 %. The NDw results were analysed in terms of the degrees of equivalence with the comparison reference values which were calculated for each beam quality as the weighted means of all results. The participant's results were consistent with the reference value within the expanded uncertainties. However, these expanded uncertainties varied significantly and ranged between about 1-1.8 % for the water calorimeter based standards and were estimated at 3.7 % for the water-graphite calorimeter. It was shown previously that the ratios NDw/NK for the type of ionization chamber used as transfer chamber in this comparison were very close (within less than 1 %) to the calculated values of (bar muen/ρ)w,ad, the mean values of the water-to-air ratio of the mass-energy-absorption coefficients at the depth d in water. Some of the participant's results deviated significantly from the expected behavior. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of

  16. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies.

    PubMed

    Ras, Rouyanne T; Geleijnse, Johanna M; Trautwein, Elke A

    2014-07-28

    Phytosterols (PS, comprising plant sterols and plant stanols) have been proven to lower LDL-cholesterol concentrations. The dose-response relationship for this effect has been evaluated in several meta-analyses by calculating averages for different dose ranges or by applying continuous dose-response functions. Both approaches have advantages and disadvantages. So far, the calculation of averages for different dose ranges has not been done for plant sterols and stanols separately. The objective of the present meta-analysis was to investigate the combined and separate effects of plant sterols and stanols when classified into different dose ranges. Studies were searched and selected based on predefined criteria. Relevant data were extracted. Average LDL-cholesterol effects were calculated when studies were categorised by dose, according to random-effects models while using the variance as weighing factor. This was done for plant sterols and stanols combined and separately. In total, 124 studies (201 strata) were included. Plant sterols and stanols were administered in 129 and fifty-nine strata, respectively; the remaining used a mix of both. The average PS dose was 2.1 (range 0.2-9.0) g/d. PS intakes of 0.6-3.3 g/d were found to gradually reduce LDL-cholesterol concentrations by, on average, 6-12%. When plant sterols and stanols were analysed separately, clear and comparable dose-response relationships were observed. Studies carried out with PS doses exceeding 4 g/d were not pooled, as these were scarce and scattered across a wide range of doses. In conclusion, the LDL-cholesterol-lowering effect of both plant sterols and stanols continues to increase up to intakes of approximately 3 g/d to an average effect of 12%.

  17. Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis: A Dose-Ranging Study

    PubMed Central

    Chavoustie, Steven E.; Jacobs, Mark; Reisman, Howard A.; Waldbaum, Arthur S.; Levy, Sharon F.; Hillier, Sharon L.; Nyirjesy, Paul

    2015-01-01

    Objective Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration–approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. Materials and Methods This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. Results In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Conclusions Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days. PMID:24983350

  18. Metronidazole vaginal gel 1.3% in the treatment of bacterial vaginosis: a dose-ranging study.

    PubMed

    Chavoustie, Steven E; Jacobs, Mark; Reisman, Howard A; Waldbaum, Arthur S; Levy, Sharon F; Hillier, Sharon L; Nyirjesy, Paul

    2015-04-01

    Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration-approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days.

  19. Effectiveness and Safety of Lower Doses of Mifepristone Combined With Misoprostol for the Termination of Ultra-Early Pregnancy: A Dose-Ranging Randomized Controlled Trial.

    PubMed

    Li, Cui-Lan; Chen, Dun-Jin; Song, Li-Ping; Wang, Yan; Zhang, Zhong-Fang; Liu, Ming-Xing; Chen, Wei-Ling

    2015-06-01

    This study aimed to investigate the effectiveness and safety of lower doses of mifepristone combined with misoprostol for the termination of ultra-early pregnancy. A total of 2500 women with ultra-early pregnancy (amenorrhea ≤ 35 days) were randomly divided into 5 groups with gradually decreased dose of oral mifepristone from 150 to 50 mg followed by 200 µg of oral misoprostol 24 hours later. The primary end point was complete abortion without surgical intervention. Secondary end points were vaginal bleeding, return of menses, and side effects. Rates of complete abortion were high in all groups. Moreover, the lower doses of mifepristone led to shorter vaginal bleeding period, the return of menses on the expected date, and fewer side effects. Lower doses of mifepristone combined with 200 µg of misoprostol are as effective and safe as higher doses of this combination for the termination of ultra-early pregnancy with lower possibility of vaginal bleeding and side effects. © The Author(s) 2014.

  20. Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

    SciTech Connect

    Zhang, Yakun; Li, Xiang; Segars, W. Paul; Samei, Ehsan

    2014-02-15

    Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definium 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDI{sub vol} and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose

  1. Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

    PubMed Central

    Zhang, Yakun; Li, Xiang; Segars, W. Paul; Samei, Ehsan

    2014-01-01

    Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definium 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDIvol and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose metrics

  2. Single-dose adjustment versus no adjustment of warfarin in stably anticoagulated patients with an occasional international normalized ratio (INR) out of range.

    PubMed

    Schulman, S; Melinyshyn, A; Ennis, D; Rudd-Scott, L

    2010-05-01

    Well-controlled patients on warfarin may still have occasional International Normalized Ratios (INRs) outside the therapeutic range. It is unclear whether there is any benefit of a single-dose correction in this situation. To evaluate whether patients with very stable INR results should continue with the maintenance dose of warfarin without a single-dose correction, even when the result unexpectedly is moderately below or above the therapeutic range. A) We reviewed retrospectively 364 patients with unchanged maintenance dose for at least 6 months and an occasional INR outside the therapeutic range regarding decision on dosing and the effect on the next INR. B) We randomized 160 patients with at least 3 months of unchanged maintenance dose, an occasional INR deviating to a minimum of 1.5 or a maximum of 4.4 and unexplained or temporary, removable cause to a single-dose Change or No change. Follow-up INRs and telephone interviews were obtained after 2 weeks. A) Retrospectively, the proportion of follow-up INRs outside the therapeutic range was 29.9% after No change, 27.1% after Increased dose and 25.7% after Skipped/reduced dose. However, the decision on No change was mainly taken in case of minimal INR deviations. B) Forty-eight (60%) of the patients randomized to Change were within the therapeutic range at follow-up versus 45 (56%) of those with No change, odds ratio 1.17 (95% confidence interval 0.59-2.30). For baseline INRs deviating down to 1.6 or up to 3.6 (therapeutic range, INR 2.0-3.0) the 2-week INRs did not differ between the groups. Our results suggest only a small or no difference between the two managements of an occasional INR out of range in terms of the 2-week follow-up INR. In stable patients on warfarin with an occasional INR outside the therapeutic range it seems reasonable to continue with the same dose without a single-dose change and perform a repeat test in about 2 weeks. (ClinicalTrials.gov number, NCT00814177.). Copyright (c) 2009 Elsevier

  3. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    PubMed

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    marrow decreased significantly. In summary, TBI in the hematopoietic ARS dose range induces substantial intestinal injury in all segments of the small bowel. These findings underscore the importance of maintaining the mucosal barrier that separates the gut microbiome from the body's interior after TBI.

  4. The suitable dose range for the calibration of EBT2 film by the PDD method with a comparison of two curve fitting algorithms

    NASA Astrophysics Data System (ADS)

    Chang, Liyun; Ho, Sheng-Yow; Lee, Tsair-Fwu; Yeh, Shyh-An; Ding, Hueisch-Jy; Chen, Pang-Yu

    2015-03-01

    EBT2 film is a convenient dosimetry quality-assurance (QA) tool with high 2D dosimetry resolution and a self-development property for use in verifications of radiation therapy treatment planning and special projects; however, the user will suffer from a relatively higher degree of uncertainty (more than ±6% by Hartmann et al. [29]), and the trouble of cutting one piece of film into small pieces and then reintegrating them each time. To prevent this tedious cutting work, and save calibration time and budget, a dose range analysis is presented in this study for EBT2 film calibration using the Percentage-Depth-Dose (PDD) method. Different combinations of the three dose ranges, 9-26 cGy, 33-97 cGy and 109-320 cGy, with two types of curve fitting algorithms, film pixel values and net optical densities converting into doses, were tested and compared. With the lowest error and acceptable inaccuracy of less than 3 cGy for the clinical dose range (9-320 cGy), a single film calibrated by the net optical density algorithm with the dose range 109-320 cGy was suggested for routine calibration.

  5. A dose-ranging study of behavioral and pharmacological treatment in social settings for children with ADHD.

    PubMed

    Pelham, William E; Burrows-MacLean, Lisa; Gnagy, Elizabeth M; Fabiano, Gregory A; Coles, Erika K; Wymbs, Brian T; Chacko, Anil; Walker, Kathryn S; Wymbs, Frances; Garefino, Allison; Hoffman, Martin T; Waxmonsky, James G; Waschbusch, Daniel A

    2014-08-01

    Placebo and three doses of methylphenidate (MPH) were crossed with 3 levels of behavioral modification (no behavioral modification, NBM; low-intensity behavioral modification, LBM; and high-intensity behavior modification, HBM) in the context of a summer treatment program (STP). Participants were 48 children with ADHD, aged 5-12. Behavior was examined in a variety of social settings (sports activities, art class, lunch) that are typical of elementary school, neighborhood, and after-school settings. Children received each behavioral condition for 3 weeks, order counterbalanced across groups. Children concurrently received in random order placebo, 0.15 mg/kg/dose, 0.3 mg/kg/dose, or 0.6 mg/kg/dose MPH, 3 times daily with dose manipulated on a daily basis in random order for each child. Both behavioral and medication treatments produced highly significant and positive effects on children's behavior. The treatment modalities also interacted significantly. Whereas there was a linear dose-response curve for medication in NBM, the dose-response curves flattened considerably in LBM and HBM. Behavior modification produced effects as large as moderate doses, and on some measures, high doses of medication. These results replicate and extend to social-recreational settings previously reported results in a classroom setting from the same sample (Fabiano et al., School Psychology Review, 36, 195-216, 2007). Results illustrate the importance of taking dosage/intensity into account when evaluating combined treatments; there were no benefits of combined treatments when the dosage of either treatment was high but combination of the low-dose treatments produced substantial incremental improvement over unimodal treatment.

  6. mFISH analysis of irradiated human fibroblasts: a comparison among radiations with different quality in the low-dose range.

    PubMed

    Berardinelli, F; Nieri, D; Tanzarella, C; Cherubini, R; De Nadal, V; Gerardi, S; Sgura, A; Antoccia, A

    2015-09-01

    The present investigation aimed to characterise the shape of dose-response curve and determining the frequency distribution of various aberration types as a function of dose and radiation quality in AG01522 primary human fibroblasts in the 0.1- to 1-Gy dose range. For this purpose, the cells were irradiated with 7.7 and 28.5 keV µm(-1) low-energy protons, 62 keV µm(-1 4)He(2+) ions (LNL Radiobiology facility) or X rays and samples collected for 24-colour mFISH analysis. X rays and 7.7 keV µm(-1) protons displayed a quadratic dose-response curve solely for total and simple exchanges, whereas for high-linear energy transfer radiations, a linear dose-response curve was observed for all the aberration categories, with the exception of complex exchanges.

  7. SU-E-J-138: On the Ion Beam Range and Dose Verification in Hadron Therapy Using Sound Waves

    SciTech Connect

    Fourkal, E; Veltchev, I; Gayou, O; Nahirnyak, V

    2015-06-15

    Purpose: Accurate range verification is of great importance to fully exploit the potential benefits of ion beam therapies. Current research efforts on this topic include the use of PET imaging of induced activity, detection of emerging prompt gamma rays or secondary particles. It has also been suggested recently to detect the ultrasound waves emitted through the ion energy absorption process. The energy absorbed in a medium is dissipated as heat, followed by thermal expansion that leads to generation of acoustic waves. By using an array of ultrasound transducers the precise spatial location of the Bragg peak can be obtained. The shape and intensity of the emitted ultrasound pulse depend on several variables including the absorbed energy and the pulse length. The main objective of this work is to understand how the ultrasound wave amplitude and shape depend on the initial ion energy and intensity. This would help guide future experiments in ionoacoustic imaging. Methods: The absorbed energy density for protons and carbon ions of different energy and field sizes were obtained using Fluka Monte Carlo code. Subsequently, the system of coupled equations for temperature and pressure is solved for different ion pulse intensities and lengths to obtain the pressure wave shape, amplitude and spectral distribution. Results: The proposed calculations show that the excited pressure wave amplitude is proportional to the absorbed energy density and for longer ion pulses inversely proportional to the ion pulse duration. It is also shown that the resulting ionoacoustic pressure distribution depends on both ion pulse duration and time between the pulses. Conclusion: The Bragg peak localization using ionoacoustic signal may eventually lead to the development of an alternative imaging method with sub-millimeter resolution. It may also open a way for in-vivo dose verification from the measured acoustic signal.

  8. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase.

    PubMed

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-19

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1-2.5 µg) conferring optimal levels of long-term expression (>10(11) photons/second/cm(2)). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>10(10) photons/second/cm(2)) was achieved at a transposon dose of 5-125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver.

  9. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase

    PubMed Central

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-01

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1–2.5 µg) conferring optimal levels of long-term expression (>1011 photons/second/cm2). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>1010 photons/second/cm2) was achieved at a transposon dose of 5–125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver. PMID:26784638

  10. [Quantitative evaluation of the anxiolytic and nootropic effects of potassium orotate in a wide range of doses].

    PubMed

    Karkishchenko, N N; Khaĭtin, M I

    1986-01-01

    Chronic administration of potassium orotate to rats per os in doses of 5, 10, 20, 50 and 100 mg/kg was followed by different correlations of the training under stress with anxiolytic activity. The doses of the drug were defined, at which the maximally pronounced effects under consideration were in optimal correlations, as were doses which entailed inhibition of the training in the presence of a relatively low tranquilizing activity, low emotional responsiveness and aggressiveness. It is suggested that natural analogs of pyrimidine, whose precursor is orotic acid, are universal endogenous regulators of mnemonic and antianxiety functions.

  11. Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

    NASA Technical Reports Server (NTRS)

    Heathcote, D. G.; Bircher, B. W.; Brown, A. H. (Principal Investigator)

    1987-01-01

    The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

  12. Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

    NASA Technical Reports Server (NTRS)

    Heathcote, D. G.; Bircher, B. W.; Brown, A. H. (Principal Investigator)

    1987-01-01

    The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

  13. Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity.

    PubMed

    Heathcote, D G; Bircher, B W

    1987-02-01

    The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev·min(-1). These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1·g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1·g follows the wellestablished pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

  14. Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity.

    PubMed

    Heathcote, D G; Bircher, B W

    1987-01-01

    The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

  15. The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure.

    PubMed

    Perez, Alfonso; Cao, Charlie

    2017-03-01

    In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d. ©2016 Wiley Periodicals, Inc.

  16. SU-E-J-146: A Research of PET-CT SUV Range for the Online Dose Verification in Carbon Ion Radiation Therapy

    SciTech Connect

    Sun, L; Hu, W; Moyers, M; Zhao, J; Hsi, W

    2015-06-15

    Purpose: Positron-emitting isotope distributions can be used for the image fusion of the carbon ion planning CT and online target verification PETCT, after radiation in the same decay period,the relationship between the same target volume and the SUV value of different every single fraction dose can be found,then the range of SUV for the radiation target could be decided.So this online range also can provide reference for the correlation and consistency in planning target dose verification and evaluation for the clinical trial. Methods: The Rando head phantom can be used as real body,the 10cc cube volume target contouring is done,beam ISO Center depth is 7.6cm and the 90 degree fixed carbon ion beams should be delivered in single fraction effective dose of 2.5GyE,5GyE and 8GyE.After irradiation,390 seconds later the 30 minutes PET-CT scanning is performed,parameters are set to 50Kg virtual weight,0.05mCi activity.MIM Maestro is used for the image processing and fusion,five 16mm diameter SUV spheres have been chosen in the different direction in the target.The average SUV in target for different fraction dose can be found by software. Results: For 10cc volume target,390 seconds decay period,the Single fraction effective dose equal to 2.5Gy,Ethe SUV mean value is 3.42,the relative range is 1.72 to 6.83;Equal to 5GyE,SUV mean value is 9.946,the relative range is 7.016 to 12.54;Equal or above to 8GyE,SUV mean value is 20.496,the relative range is 11.16 to 34.73. Conclusion: Making an evaluation for accuracy of the dose distribution using the SUV range which is from the planning CT with after treatment online PET-CT fusion for the normal single fraction carbon ion treatment is available.Even to the plan which single fraction dose is above 2GyE,in the condition of other parameters all the same,the SUV range is linearly dependent with single fraction dose,so this method also can be used in the hyper-fraction treatment plan.

  17. SU-E-T-117: Dose to Organs Outside of CT Scan Range- Monte Carlo and Hybrid Phantom Approach

    SciTech Connect

    Pelletier, C; Jung, J; Lee, C; Kim, J; Lee, C

    2014-06-01

    Purpose: Epidemiological study of second cancer risk for cancer survivors often requires the dose to normal tissues located outside the anatomy covered by radiological imaging, which is usually limited to tumor and organs at risk. We have investigated the feasibility of using whole body computational human phantoms for estimating out-of-field organ doses for patients treated by Intensity Modulated Radiation Therapy (IMRT). Methods: Identical 7-field IMRT prostate plans were performed using X-ray Voxel Monte Carlo (XVMC), a radiotherapy-specific Monte Carlo transport code, on the computed tomography (CT) images of the torso of an adult male patient (175 cm height, 66 kg weight) and an adult male hybrid computational phantom with the equivalent body size. Dose to the liver, right lung, and left lung were calculated and compared. Results: Considerable differences are seen between the doses calculated by XVMC for the patient CT and the hybrid phantom. One major contributing factor is the treatment method, deep inspiration breath hold (DIBH), used for this patient. This leads to significant differences in the organ position relative to the treatment isocenter. The transverse distances from the treatment isocenter to the inferior border of the liver, left lung, and right lung are 19.5cm, 29.5cm, and 30.0cm, respectively for the patient CT, compared with 24.3cm, 36.6cm, and 39.1cm, respectively, for the hybrid phantom. When corrected for the distance, the mean doses calculated using the hybrid phantom are within 28% of those calculated using the patient CT. Conclusion: This study showed that mean dose to the organs located in the missing CT coverage can be reconstructed by using whole body computational human phantoms within reasonable dosimetric uncertainty, however appropriate corrections may be necessary if the patient is treated with a technique that will significantly deform the size or location of the organs relative to the hybrid phantom.

  18. Safety, efficacy, and dose response of fluticasone propionate delivered via the novel MDPI in patients with severe asthma: A randomized, controlled, dose-ranging study.

    PubMed

    Bernstein, David I; Gillespie, Michael; Song, Sharon; Steinfeld, Jonathan

    2017-08-01

    Evaluate fluticasone propionate (Fp) using a novel, inhalation-driven, multidose dry powder inhaler (MDPI) in patients with severe persistent asthma, versus placebo MDPI and Fp dry powder inhaler (DPI). Patients with persistent asthma despite use of high-dose inhaled corticosteroids were randomized to Fp MDPI 50, 100, 200, or 400 mcg; Fp DPI 250 mcg; or placebo MDPI twice daily for 12 weeks. The primary outcome measure was change from baseline in trough forced expiratory volume in 1 second (FEV1) over the 12-week period, compared with placebo; secondary measures included change from baseline in peak expiratory flow (PEF), rescue inhaler use, and time to withdrawal due to meeting stopping criteria. Safety included adverse events and laboratory evaluations. Six hundred forty patients were randomized; 459 (72%) completed the study. Numerical dose-related improvements in FEV1 were observed in all Fp MDPI groups over 12 weeks but were not significantly greater versus placebo. Increases in morning PEF (baseline to week 12) were substantially greater than placebo in all Fp MDPI groups. The Fp MDPI and Fp DPI groups had substantial reductions in rescue inhaler use from baseline to end point versus placebo (p ≤ 0.05). Efficacy was comparable between Fp MDPI and Fp DPI. No new safety signals were detected; the safety profile of Fp MDPI was similar to that of Fp DPI. Clinical benefit observed with Fp MDPI in patients with persistent asthma was comparable to Fp DPI. Safety was reassuring with no unexpected findings. These results support further evaluation of Fp MDPI in asthma. (ClinicalTrials.gov identifier NCT01576718; EudraCT number 2010-023601-35).

  19. A randomized, controlled, dose-ranging study investigating single doses of GW406381, naproxen sodium, or placebo in patients with acute pain after third molar tooth extraction.

    PubMed

    Varner, Julie; Lomax, Mark; Blum, David; Quessy, Steve

    2009-09-01

    To evaluate the efficacy and tolerability of 4 doses of GW406381, a cyclooxygenase-2 inhibitor, compared with placebo in a standard model of acute inflammatory pain. This randomized, double-blind, placebo-controlled, single-center study compared single doses of GW406381 (10 to 70 mg) or naproxen sodium 550 mg with placebo in patients after extraction of 2 or more partially bony impacted third molar teeth. A total of 300 patients were randomized (50 per group). The primary efficacy variable was the pain relief intensity difference score at each time point, which was calculated as the sum of the pain intensity difference and pain relief categorical scores at each time point. Each treatment was compared with placebo at each time point using an ordered hierarchical approach with closed testing procedures and last observation carried forward imputation methods. Pain relief intensity differences from placebo were statistically significant beginning at 1.5 hours postdosing for GW406381 70 and 50 mg and at 2-hour postdosing for GW406381 25 and 10 mg. The median time to onset of analgesia was 71 minutes for GW406381 50 mg, 72 minutes for GW406381 70 mg, and 36 minutes for naproxen. The median duration of analgesia was 5.9 hours for GW406381 50 mg, 7.9 hours for GW406391 70 mg, and 11.3 hours for naproxen. All treatments were well tolerated. GW406381 50 and 70 mg demonstrated clinically meaningful analgesia in this acute pain setting, although the onset of analgesia was greater than 1 hour.

  20. Dose-ranging study of the performance of the natural oxygen transporter HEMO2 Life in organ preservation.

    PubMed

    Mallet, Vanessa; Dutheil, Delphine; Polard, Valérie; Rousselot, Morgane; Leize, Elisabeth; Hauet, Thierry; Goujon, Jean Michel; Zal, Franck

    2014-08-01

    The intensity of ischemia-reperfusion injury of the donor organ during the preservation phase and after anastomosis is acknowledged as being a key factor for long-term graft outcome. We previously showed that the addition of 5 g/L of the natural oxygen carrier HEMO2 Life was beneficial for the cold static preservation of kidney grafts in both University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate solutions. Herein, we refined these findings by evaluating HEMO2 Life at various dose levels in UW, both in vitro with endothelial cells and in vivo in a pig kidney autotransplantation preclinical model. We showed in vitro that cells were significantly better preserved with HEMO2 Life in a dose-dependent manner, with benefits in terms of survival, metabolic activity, and cellular integrity. In vivo, serum creatinine measurements at reperfusion confirmed the important benefits of HEMO2 Life treatment on function recovery at the dose levels of 1, 2, and 5 g/L. Likewise, histological analysis of kidney parenchyma biopsies from day 7 confirmed the superiority of HEMO2 Life-supplemented UW over UW alone, and there was no difference between the doses. Three months' follow-up confirmed the trend of the first 2 weeks, with creatinine and fibrosis levels similar to those in pretransplant kidneys. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  1. Epidural dexamethasone for post-operative analgesia in patients undergoing abdominal hysterectomy: A dose ranging and safety evaluation study

    PubMed Central

    Hefni, Amira Fathy; Mahmoud, Mohamed Sidky; Al Alim, Azza Atef Abd

    2014-01-01

    Aim: Number of studies revealed that epidural bupivacaine-dexamethasone has the same analgesic potency as bupivacaine-fentanyl with opioid sparing and antiemetic effects. Different doses of dexamethasone were used in different studies. This study was designed to evaluate the optimum dose of epidural dexamethasone for post-operative analgesia. Materials and Methods: In this double-blinded randomized controlled study, we evaluated the efficiency and safety of different doses of epidural dexamethasone for post-operative analgesia in 160 patients aged 45-60 years scheduled for total abdominal hysterectomy. Patient were randomly allocated into four groups to receive a total volume of 10 ml epidural plain bupivacaine 0.25% in the control group (Group D0) with either 4 mg dexamethasone in (Group D4) or 6 mg dexamethasone in (Group D6) or 8 mg dexamethasone in (Group D8). Patients then received general anesthesia. Sedation, satisfaction and visual analog pain scores (VAS) at rest and with effort were measured post-operatively. Meperidine was administered when VAS > or = 4. Intra-operative fentanyl dose, post-operative meperidine consumption and the time to first analgesic requirement were recorded by a blinded observer. Blood glucose was measured pre-operatively and at 4 h and 8 h after study drug administration. Wound healing and infection were assessed after 1 week. Results: Intraoperative fentanyl requirements were comparable among groups. The time to first analgesic requirement was significantly prolonged 5.5 times in D8 Group but only 1.5 times in D6 and D4 Groups more than the analgesic duration in the control Group D0, with a P < 0.01. There was a significant reduction in post-operative meperidine consumption during the first 24 h in the D8 (75%) in comparison with D6 and D4 Groups (50%), respectively, (P < 0.01) and the control Group D0 (0%) (P < 0.01). VAS scores were significantly lower and patient satisfaction score was significantly higher in the D8 and

  2. The impact of uncertainties in the CT conversion algorithm when predicting proton beam ranges in patients from dose and PET-activity distributions.

    PubMed

    España, Samuel; Paganetti, Harald

    2010-12-21

    The advantages of a finite range of proton beams can only be partly exploited in radiation therapy unless the range can be predicted in patient anatomy with <2 mm accuracy (for non-moving targets). Monte Carlo dose calculation aims at 1-2 mm accuracy in dose prediction, and proton-induced PET imaging aims at ∼2 mm accuracy in range verification. The latter is done using Monte Carlo predicted PET images. Monte Carlo methods are based on CT images to describe patient anatomy. The dose calculation algorithm and the CT resolution/artifacts might affect dose calculation accuracy. Additionally, when using Monte Carlo for PET range verification, the biological decay model and the cross sections for positron emitter production affect predicted PET images. The goal of this work is to study the effect of uncertainties in the CT conversion on the proton beam range predicted by Monte Carlo dose calculations and proton-induced PET signals. Conversion schemes to assign density and elemental composition based on a CT image of the patient define a unique Hounsfield unit (HU) to tissue parameters relationship. Uncertainties are introduced because there is no unique relationship between HU and tissue parameters. In this work, different conversion schemes based on a stoichiometric calibration method as well as different numbers of tissue bins were considered in three head and neck patients. For Monte Carlo dose calculation, the results show close to zero (<0.5 mm) differences in range using different conversion schemes. Further, a reduction of the number of bins used to define individual tissues down to 13 did not affect the accuracy. In the case of simulated PET images we found a more pronounced sensitivity on the CT conversion scheme with a mean fall-off position variation of about 1 mm. We conclude that proton dose distributions based on Monte Carlo calculation are only slightly affected by the uncertainty on density and elemental composition introduced by unique assignment to

  3. EBT2 film as a depth-dose measurement tool for radiotherapy beams over a wide range of energies and modalities

    SciTech Connect

    Arjomandy, Bijan; Tailor, Ramesh; Zhao Li; Devic, Slobodan

    2012-02-15

    Purpose: One of the fundamental parameters used for dose calculation is percentage depth-dose, generally measured employing ionization chambers. There are situations where use of ion chambers for measuring depth-doses is difficult or problematic. In such cases, radiochromic film might be an alternative. The EBT-2 model GAFCHROMIC film was investigated as a potential tool for depth-dose measurement in radiotherapy beams over a broad range of energies and modalities. Methods: Pieces of the EBT-2 model GAFCHROMIC EBT2 film were exposed to x-ray, electron, and proton beams used in radiotherapy. The beams employed for this study included kilovoltage x-rays (75 kVp), {sup 60}Co gamma-rays, megavoltage x-rays (18 MV), electrons (7 and 20 MeV), and pristine Bragg-peak proton beams (126 and 152 MeV). At each beam quality, film response was measured over the dose range of 0.4-8.0 Gy, which corresponds to optical densities ranging from 0.05 to 0.4 measured with a flat-bed document scanner. To assess precision in depth-dose measurements with the EBT-2 model GAFCHROMIC film, uncertainty in measured optical density was investigated with respect to variation in film-to-film and scanner-bed uniformity. Results: For most beams, percentage depth-doses measured with the EBT-2 model GAFCHROMIC film show an excellent agreement with those measured with ion chambers. Some discrepancies are observed in case of (i) kilovoltage x-rays at larger depths due to beam-hardening, and (ii) proton beams around Bragg-peak due to quenching effects. For these beams, an empirical polynomial correction produces better agreement with ion-chamber data. Conclusions: The EBT-2 model GAFCHROMIC film is an excellent secondary dosimeter for measurement of percentage depth-doses for a broad range of beam qualities and modalities used in radiotherapy. It offers an easy and efficient way to measure beam depth-dose data with a high spatial resolution.

  4. Prasugrel in children with sickle cell disease: pharmacokinetic and pharmacodynamic data from an open-label, adaptive-design, dose-ranging study.

    PubMed

    Styles, Lori; Heiselman, Darell; Heath, Lori E; Moser, Brian A; Small, David S; Jakubowski, Joseph A; Zhou, Chunmei; Redding-Lallinger, Rupa; Heeney, Matthew M; Quinn, Charles T; Rana, Sohail R; Kanter, Julie; Winters, Kenneth J

    2015-01-01

    This phase 2 study was designed to characterize the relationship among prasugrel dose, prasugrel's active metabolite (Pras-AM), and platelet inhibition while evaluating safety in children with sickle cell disease. It was open-label, multicenter, adaptive design, dose ranging, and conducted in 2 parts. Part A: Patients received escalating single doses leading to corresponding increases in Pras-AM exposure and VerifyNow®P2Y12 (VN) platelet inhibition and decreases in VNP2Y12 reaction units and vasodilator-stimulated phosphoprotein platelet reactivity index. Part B: Patients were assigned daily doses (0.06, 0.08, and 0.12 mg/kg) based on VN pharmacodynamic measurements at the start of 2 dosing periods, each 14±4 days. Platelet inhibition was significantly higher at 0.12 mg/kg (56.3%±7.4%; least squares mean±SE) compared with 0.06 mg/kg (33.8%±7.4%) or 0.08 mg/kg (37.9%±5.6%). Patients receiving 0.12 mg/kg achieved ≥30% platelet inhibition; only 1 patient receiving 0.06 mg/kg exceeded 60% platelet inhibition. High interpatient variability in response to prasugrel and the small range of exposures precluded rigorous characterization of the relationship among dose, Pras-AM, and platelet inhibition. No hemorrhagic events occurred in Part A; 3 occurred in Part B, all mild and self-limited. Most children with sickle cell disease may achieve clinically relevant platelet inhibition with titration of daily-dose prasugrel.

  5. Evaluation of GAFCHROMIC EBT2 dosimetry for the low dose range using a flat-bed scanner with the reflection mode.

    PubMed

    Gotanda, Tatsuhiro; Katsuda, Toshizo; Akagawa, Takuya; Gotanda, Rumi; Tabuchi, Akihiko; Yamamoto, Kenyu; Kuwano, Tadao; Yatake, Hidetoshi; Yabunaka, Koichi; Takeda, Yoshihiro

    2013-03-01

    Recently developed radiochromic films can easily be used to measure absorbed doses because they do not need development processing and indicate a density change that depends on the absorbed dose. However, in GAFCHROMIC EBT2 dosimetry (GAF-EBT2) as a radiochromic film, the precision of the measurement was compromised, because of non-uniformity problems caused by image acquisition using a flat-bed scanner with a transmission mode. The purpose of this study was to improve the precision of the measurement using a flat-bed scanner with a reflection mode at the low absorbed dose dynamic range of GAF-EBT2. The calibration curves of the absorbed dose versus the film density for GAF-EBT2 were provided. X-rays were exposed in the range between ~0 and 120 mGy in increments of about 12 mGy. The results of the method using a flat-bed scanner with the transmission mode were compared with those of the method using the same scanner with the reflection mode. The results should that the determination coefficients (r (2) ) for the straight-line approximation of the calibration curve using the reflection mode were higher than 0.99, and the gradient using the reflection mode was about twice that of the one using the transmission mode. The non-uniformity error that is produced by a flat-bed scanner with the transmission mode setting could be almost eliminated by converting from the transmission mode to the reflection mode. In light of these findings, the method using a flat-bed scanner with the reflection mode (only using uniform white paper) improved the precision of the measurement for the low absorbed dose range.

  6. A 24-week multicenter, randomized, double-blind, parallel-group, dose-ranging study of rufinamide in adults and adolescents with inadequately controlled partial seizures.

    PubMed

    Elger, Christian E; Stefan, Hermann; Mann, Allison; Narurkar, Milind; Sun, Yijun; Perdomo, Carlos

    2010-02-01

    To assess the efficacy, safety, tolerability, and pharmacokinetics of adjunctive rufinamide in adults and adolescents with inadequately controlled partial seizures receiving treatment with one to three concomitant antiepileptic drugs (AEDs). A 24-week multicenter Phase II clinical study was conducted (n=647), comprising a 12-week prospective baseline phase and a 12-week randomized double-blind, parallel-group, five-arm (placebo and rufinamide 200, 400, 800, and 1600mg/day) treatment phase. The linear trend of dose response for seizure frequency per 28 days in the double-blind treatment phase - the primary efficacy outcome measure - was statistically significant in favor of rufinamide (estimated slope=-0.049, P=0.003; minimally efficacious dose, 400mg/day). Response rates, defined as a >or=50% reduction in seizure frequency per 28 days, also revealed a significant linear trend of dose response (P=0.0019, logistic regression analysis). Adverse events were comparable between placebo and all rufinamide groups except the 1600mg/day group; no safety signals were observed. These results suggest that in the dose range of 400-1600mg/day, add-on rufinamide therapy may benefit patients with inadequately controlled partial seizures and is generally well tolerated. These data also suggest that higher doses may confer additional efficacy without adversely affecting safety and tolerability.

  7. Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection

    PubMed Central

    Lucasti, Christopher; Vasile, Liviu; Sandesc, Dorel; Venskutonis, Donatas; McLeroth, Patrick; Lala, Mallika; Rizk, Matthew L.; Brown, Michelle L.; Losada, Maria C.; Pedley, Alison; Kartsonis, Nicholas A.

    2016-01-01

    Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas. In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains. PMID:27503659

  8. Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus.

    PubMed

    Kiyosue, A; Hayashi, N; Komori, H; Leonsson-Zachrisson, M; Johnsson, E

    2013-10-01

    To assess the glucose-lowering effects of monotherapy with the glucokinase activator AZD1656 in Japanese patients with type 2 diabetes mellitus. This was a randomized, double-blind, placebo-controlled study performed in Japan (NCT01152385). Patients (n = 224) were randomized to AZD1656 (40-200, 20-140 or 10-80 mg titrated doses) or placebo. The primary variable was the placebo-corrected change from baseline to 4 months in glycated haemoglobin (HbA1c). Effects on fasting plasma glucose (FPG) and safety were also assessed. HbA1c was reduced numerically from baseline by 0.3-0.8% with AZD1656 and by 0.1% with placebo over the first 2 months of treatment, after which effects of AZD1656 started to decline. The changes from baseline to 4 months in HbA1c were not significant for the AZD1656 40-200 mg group versus placebo [mean (95% CI) placebo-corrected change: -0.22 (-0.65, 0.20)%; p = 0.30]. Formal significance testing was not carried out for the other two AZD1656 dose groups. A higher percentage of patients on AZD1656 achieved HbA1c ≤ 7% after 4 months versus placebo, but responder rates were low. Results for FPG reflected those for HbA1c. Cases of hypoglycaemia were rare with AZD1656 (one patient) and no safety concerns were raised. Although initially favourable plasma glucose reductions were observed, there was a loss of effect over time with sustained AZD1656 treatment. The study design did not allow an evaluation of the reasons for this lack of long-term efficacy. © 2013 John Wiley & Sons Ltd.

  9. Calculated absorbed-dose ratios, TG51/TG21, for most widely used cylindrical and parallel-plate ion chambers over a range of photon and electron energies.

    PubMed

    Tailor, R C; Hanson, W F

    2002-07-01

    Task Group 51 (TG51), of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM), has developed a calibration protocol for high-energy photon and electron therapy beams based on absorbed dose standards. This protocol is intended to replace the air-kerma based protocol developed by an earlier AAPM task group (TG21). Conversion to the newer protocol introduces a change in the determined absorbed dose. In this work, the change in dose is expressed as the ratio of the doses (TG51/TG21) based on the two protocols. Dose is compared at the TG-51 reference depths of 10 cm for photons and d(ref) for electrons. Dose ratios are presented for a variety of ion chambers over a range of photon and electron energies. The TG51/TG21 dose ratios presented here are based on the dosimetry factors provided by the two protocols and the chamber-specific absorbed dose and exposure calibration factors (N60Co(D,w) and Nx) provided by the Accredited Dosimetry Calibration Laboratory (ADCL) at The University of Texas, M. D. Anderson Cancer Center (MDACC). As such, the values presented here represent the expected discrepancies between the two protocols due only to changes in the dosimetry parameters and the differences in chamber-specific dose and air-kerma standards. These values are independent of factors such as measurement uncertainties, setup errors, and inconsistencies arising from the mix of different phantoms and ion chambers for the two protocols. Therefore, these ratios may serve as a guide for institutions performing measurements for the switch from TG21-to-TG51 based calibration. Any significant deviation in the ratio obtained from measurements versus those presented here should prompt a review to identify possible errors and inconsistencies. For all cylindrical chambers included here, the TG51/TG21 dose ratios are the same within +/-0.6%, irrespective of the make and model of the chamber, for each photon and electron beam included. Photon beams

  10. Dose-ranging pilot randomized trial of amino acid mixture combined with physical activity promotion for reducing abdominal fat in overweight adults

    PubMed Central

    Sasai, Hiroyuki; Ueda, Keisuke; Tsujimoto, Takehiko; Kobayashi, Hiroyuki; Sanbongi, Chiaki; Ikegami, Shuji; Nakata, Yoshio

    2017-01-01

    Objective The objective of this study was to determine the effective dose of an amino acid mixture comprising arginine, alanine, and phenylalanine combined with physical activity promotion in reducing abdominal fat among overweight adults. Methods A 12-week randomized, double-blind, placebo-controlled, dose-ranging, pilot trial was conducted in Mito, Japan, from January through April 2016, and the data were analyzed from May through November 2016. The study participants were 35 overweight adults, aged 20–64 years, with no regular exercise habit. Participants were randomly assigned to high-dose (3,000 mg/d, n=9), medium-dose (1,500 mg/d, n=9), low-dose (750 mg/d, n=8), or placebo (0 mg/d, n=9) groups, and the test beverage containing the amino acid mixture or placebo was administered for 12 weeks. All participants maintained a physically active lifestyle during the study period through monthly physical activity promotion sessions and smartphone-based self-monitoring with wearable trackers. Primary outcomes were changes in abdominal total, subcutaneous, and visceral fat areas, assessed by computed tomography. Results Of the 35 enrolled participants, 32 completed the 12-week follow-up visit. The intention-to-treat analysis revealed that the changes in abdominal total fat area were −14.6 cm2 (95% confidence interval [CI], −39.6 cm2 to 10.4 cm2), −25.3 cm2 (95% CI, −71.0 cm2 to 20.3 cm2), −23.2 cm2 (95% CI, −48.0 cm2 to 1.6 cm2), and −12.5 cm2 (95% CI, −29.1 cm2 to 4.0 cm2) in the high-dose, medium-dose, low-dose, and placebo groups, respectively. Similar results were obtained for visceral and subcutaneous fat areas. No study-related adverse events were reported. Conclusion Compared with placebo, a medium or low dose of the amino acid mixture may facilitate abdominal fat reduction among overweight adults. A larger randomized trial with sufficient statistical power should be implemented to validate the effectiveness of this supplement. PMID:28740413

  11. Evaluation of microdosing strategies for studies in preclinical drug development: demonstration of linear pharmacokinetics in dogs of a nucleoside analog over a 50-fold dose range.

    PubMed

    Sandhu, Punam; Vogel, John S; Rose, Mark J; Ubick, Esther A; Brunner, Janice E; Wallace, Michael A; Adelsberger, Jennifer K; Baker, Maribeth P; Henderson, Paul T; Pearson, Paul G; Baillie, Thomas A

    2004-11-01

    The technique of accelerator mass spectrometry (AMS) was validated successfully and used to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate (7-deaza-2'-C-methyl-adenosine; Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across subpharmacological (microdose) and pharmacological dose ranges in an animal model, before initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as liquid chromatography-tandem mass spectrometry and liquid scintillation counting analyses. Compound A displayed multiphasic kinetics and exhibited low plasma clearance (5.8 ml/min/kg), a long terminal elimination half-life (17.5 h), and high oral bioavailability (103%). Currently, there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus subpharmacological doses using microdosing strategies. The present study thus provides the first description of the full pharmacokinetic profile of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A following dosing at 0.02 mg/kg were similar to those at 1 mg/kg, indicating that in the case of Compound A, the pharmacokinetics in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even after a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques.

  12. Randomized, dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids.

    PubMed

    Kerwin, Edward M; Gillespie, Michael; Song, Sharon; Steinfeld, Jonathan

    2017-01-02

    A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators. This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1). Blood samples were collected from a patient subset to evaluate pharmacokinetics. Adverse events were monitored. Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV1 over 12 weeks compared with placebo (p < 0.01). There were no substantial differences in FEV1 change from baseline over 12 weeks between any Fp MDPI dose and Fp DPI 100 µg. Maximum observed concentration (Cmax) of Fp increased with increasing Fp MDPI doses; time of Cmax was similar across doses and treatments. Systemic exposures for Fp MDPI 25 and 50 µg were lower than that for Fp DPI 100 µg. The safety profile of Fp MDPI was consistent with that of Fp DPI. In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.

  13. Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study

    PubMed Central

    Johnson, Casey; Hohenboken, Matthew; Poling, Terry; Jaehnig, Peter; Kanesa-thasan, Niranjan

    2015-01-01

    Background. A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important. Methods. In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data. Results. Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3–<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate. Conclusions. A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations. Clinical Trials Registration. ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945). PMID:25538277

  14. Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial.

    PubMed

    Bone, Henry G; Kiel, Douglas P; Lindsay, Robert S; Lewiecki, E Michael; Bolognese, Michael A; Leary, Elizabeth T; Lowe, Wing; McClung, Michael R

    2007-12-01

    In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk. Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women. We conducted a prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial at 62 sites in the United States. Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), and lumbar (L1-L4) spine bone mineral density T-score between 0.0 and -2.5. Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin was administered. We assessed percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo. At 52 wk, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo. Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis.

  15. A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum.

    PubMed

    Hale, Braden R; Owusu-Agyei, Seth; Fryauff, David J; Koram, Kwadwo A; Adjuik, Martin; Oduro, Abraham R; Prescott, W Roy; Baird, J Kevin; Nkrumah, Francis; Ritchie, Thomas L; Franke, Eileen D; Binka, Fred N; Horton, John; Hoffman, Stephen L

    2003-03-01

    Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, double-blind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%-43%); for 50 mg/week, 84% (95% CI, 75%-91%); for 100 mg/week, 87% (95% CI, 78%-93%); and for 200 mg/week, 86% (95% CI, 76%-92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%-93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population.

  16. Radiological dose assessment for residual radioactive material in soil at the clean slate sites 1, 2, and 3, Tonopah Test Range

    SciTech Connect

    1997-06-01

    A radiological dose assessment has been performed for Clean Slate Sites 1, 2, and 3 at the Tonopah Test Range, approximately 390 kilometers (240 miles) northwest of Las Vegas, Nevada. The assessment demonstrated that the calculated dose to hypothetical individuals who may reside or work on the Clean Slate sites, subsequent to remediation, does not exceed the limits established by the US Department of Energy for protection of members of the public and the environment. The sites became contaminated as a result of Project Roller Coaster experiments conducted in 1963 in support of the US Atomic Energy Commission (Shreve, 1964). Remediation of Clean Slate Sites 1, 2, and 3 is being performed to ensure that the 50-year committed effective dose equivalent to a hypothetical individual who lives or works on a Clean Slate site should not exceed 100 millirems per year. The DOE residual radioactive material guideline (RESRAD) computer code was used to assess the dose. RESRAD implements the methodology described in the DOE manual for establishing residual radioactive material guidelines (Yu et al., 1993a). In May and June of 1963, experiments were conducted at Clean Slate Sites 1, 2, and 3 to study the effectiveness of earth-covered structures for reducing the dispersion of nuclear weapons material as a result of nonnuclear explosions. The experiments required the detonation of various simulated weapons using conventional chemical explosives (Shreve, 1964). The residual radioactive contamination in the surface soil consists of weapons grade plutonium, depleted uranium, and their radioactive decay products.

  17. Equivalent asthma control and systemic safety of inhaled budesonide delivered via HFA-134a or CFC propellant in a broad range of doses.

    PubMed

    Grzelewska-Rzymowska, I; Malolepszy, J; de Molina, M; Sladek, K; Zarkovice, J; Siergiejko, Z

    2003-11-01

    was also noted with both propellants. In conclusion, the budesonide HFA-134a formulation given with a spacer device provided an equivalent asthma control with that of a corresponding CFC product, when administered in stable patients treated with inhaled corticosteroids in a broad range of daily doses. The use of the new propellant did not modify the safety profile of inhaled budesonide.

  18. Dose-ranging study of salmeterol using a novel fluticasone propionate/salmeterol multidose dry powder inhaler in patients with persistent asthma.

    PubMed

    Miller, David S; Yiu, Gloria; Hellriegel, Edward T; Steinfeld, Jonathan

    2016-07-01

    New inhalation devices with improved lung delivery may allow the use of lower salmeterol doses for treatment of asthma. To determine the dose of salmeterol administered from a novel fluticasone propionate/salmeterol (FS) inhalation-driven, multidose dry powder inhaler (MDPI), which provides comparable efficacy and safety to FS dry powder inhaler (DPI). This double-blind, six-period crossover, dose-ranging study randomized 72 patients (ages ≥12 years; with persistent asthma and predose maximum forced expiratory volume in 1 second [FEV1] of 40-85% of the predicted normal) to treatment sequences (one dose per treatment), which consisted of FS MDPI 100/6.25, 100/12.5, 100/25, 100/50 μg; fluticasone propionate (Fp) MDPI 100 μg; and open-label FS DPI 100/50 μg. The primary efficacy variable was the baseline-adjusted FEV1 area under the curve over 12 hours after the dose (AUC0-12). Pharmacokinetics and tolerability were also assessed. FEV1 AUC0-12 was significantly higher with all FS MDPI doses and FS DPI versus Fp MDPI (p < 0.0001), and with FS MDPI 100/50 μg versus FS DPI (least squares [LS] mean, 57.88 mL; p = 0.0017). FEV1 AUC0-12 trended toward higher efficacy with FS MDPI 100/25 μg (LS mean, 34.14 mL; p = 0.0624) and was comparable with FS MDPI 100/12.5 μg (LS mean, 3.42 mL; p = 0.8503) versus FS DPI. Salmeterol area under the plasma concentration-versus-time curve from time 0 to the time of the last measurable concentration (AUC0-t) for FS MDPI 100/12.5 μg and 100/25 μg was lower versus FS DPI 100/50 μg; AUC0-t for FS MDPI 100/50 μg was higher than FS DPI 100/50 μg. All FS MDPI doses were generally well tolerated. All FS MDPI doses produced greater efficacy versus Fp MDPI. FS MDPI 100/12.5 μg demonstrated similar efficacy to FS DPI 100/50 μg with less salmeterol exposure. Clinicaltrials.gov NCT02139644, NCT02175771, and NCT02141854.

  19. Effect of Gamma Irradiation on Cement Composites Observed with XRD and SEM Methods in the Range of Radiation Dose 0-1409 MGy

    NASA Astrophysics Data System (ADS)

    Łowińska-Kluge, A.; Piszora, P.

    2008-08-01

    The effect of gamma radiation in the range of 0-1409 MGy on the structure of a new mineral additive to cement based composites was investigated in the perspective of employing them as radioactive waste protection material. According to the authors knowledge, it is the first paper dealing with observations of the cement matrix, both pure and modified, treated with so giant radiation dose. The absorption of gamma radiation modifies the morphology of the additive grains, causes decomposition of cement hydrates and clinker relicts in cement paste containing the additive at twice higher radiation dose than that inducing the decomposition of the reference pure cement paste and the cement paste containing pozzolane additives.

  20. A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta-blockade and steady-state pharmacokinetics.

    PubMed Central

    Ishizaki, T; Oyama, Y; Suganuma, T; Sasaki, T; Nakaya, H; Shibuya, T; Sato, T

    1983-01-01

    The relationship between the oral dosage and plasma concentration of the long-acting cardioselective beta-adrenoceptor blocker atenolol and the antihypertensive response to the the degree of beta-adrenoceptor blockade and change in plasma renin activity (PRA) was evaluated in patients with mild-to-moderate essential hypertension in a double-blind, randomized, between-patient, dose-ranging (25, 50 or 100 mg once daily for 4 weeks) study. The optimum, or minimum, daily dose of atenolol to treat patients with mild-to-moderate hypertension was not clearly identified in this study. A between-treatment comparison did not demonstrate that all blood pressure falls were always less in the 25 mg group than in the other two groups. Calculation of beta-error or the power for the negative results between doses suggested that a large sample size is required to draw a conclusion that no dose-antihypertensive relationship of atenolol exists in the treatment of mild-to-moderate hypertension. A relatively flat plasma concentration-antihypertensive response relationship was observed. Steady-state plasma concentrations of atenolol were dose-related and renal drug clearance was well correlated with individual creatinine clearance. beta-adrenoceptor blockade was better correlated with plasma atenolol concentration. Correlations which were less strong were between plasma drug concentration and change in various blood pressures and between blood pressure falls and beta-adrenoceptor blockade. There was no relationship between the fall in blood pressure and change in PRA. Atenolol appeared to suppress PRA in an all-or-none fashion. PMID:6349668

  1. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.

    PubMed

    Besarab, Anatole; Provenzano, Robert; Hertel, Joachim; Zabaneh, Raja; Klaus, Stephen J; Lee, Tyson; Leong, Robert; Hemmerich, Stefan; Yu, Kin-Hung Peony; Neff, Thomas B

    2015-10-01

    Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects. NDD-CKD subjects with hemoglobin (Hb) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity. Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo. Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. Clintrials.gov #NCT00761657. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA.

  2. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients

    PubMed Central

    Besarab, Anatole; Provenzano, Robert; Hertel, Joachim; Zabaneh, Raja; Klaus, Stephen J.; Lee, Tyson; Leong, Robert; Hemmerich, Stefan; Yu, Kin-Hung Peony; Neff, Thomas B.

    2015-01-01

    Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects. Methods NDD-CKD subjects with hemoglobin (Hb) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity. Results Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo. Conclusions Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. Clinical Trials Registration Clintrials.gov #NCT00761657. PMID:26238121

  3. What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport®

    PubMed Central

    Poewe, W; Deuschl, G; Nebe, A; Feifel, E; Wissel, J; Benecke, R; Kessler, K; Ceballos-Baumann, A; Ohly, A; Oertel, W; Kunig, G

    1998-01-01

    OBJECTIVES—Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations.
METHODS—Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport® units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4,and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect.
RESULTS—seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p<0.05). Additionally positive dose-response relations were found for the degree of subjective improvement, duration of improvement, improvement on clinical global rating, and need for reinjection at eight weeks. A significant dose relation was also established for the number of adverse events overall and for the incidence of neck muscle weakness and voice changes.
CONCLUSION—Magnitude and duration of improvement was greatest after injections of 1000 units Dysport®; however, at the cost of significantly more adverse events. Therefore a lower starting dose of 500 units Dysport® is

  4. Energy dependence and dose response of Gafchromic EBT2 film over a wide range of photon, electron, and proton beam energies

    SciTech Connect

    Arjomandy, Bijan; Tailor, Ramesh; Anand, Aman; Sahoo, Narayan; Gillin, Michael; Prado, Karl; Vicic, Milos

    2010-05-15

    Purpose: Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characterization, especially energy dependence, has become critically important. The energy dependence of the dose response of Gafchromic EBT2 film is evaluated for a broad range of energies from different radiation sources used in radiation therapy. Methods: The beams used for this study comprised of kilovoltage x rays (75, 125, and 250 kVp), {sup 137}Cs gamma (662 KeV), {sup 60}Co gamma (1.17-1.33 MeV), megavoltage x rays (6 and 18 MV), electron beams (6 and 20 MeV), and proton beams (100 and 250 MeV). The film's response to each of the above energies was measured over the dose range of 0.4-10 Gy, which corresponds to optical densities ranging from 0.05 to 0.74 for the film reader used. Results: The energy dependence of EBT2 was found to be relatively small within measurement uncertainties (1{sigma}={+-}4.5%) for all energies and modalities. Conclusion: For relative and absolute dosimetry of radiation therapy beams, the weak energy dependence of the EBT2 makes it most suitable for clinical use compared to other films.

  5. Efficacy and safety of oxantel pamoate in school-aged children infected with Trichuris trichiura on Pemba Island, Tanzania: a parallel, randomised, controlled, dose-ranging study.

    PubMed

    Moser, Wendelin; Ali, Said M; Ame, Shaali M; Speich, Benjamin; Puchkov, Maxim; Huwyler, Jörg; Albonico, Marco; Hattendorf, Jan; Keiser, Jennifer

    2016-01-01

    %]) after treatment. Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura. An optimum therapeutic dose range of 15-30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7-14 years in sub-Saharan Africa would receive doses of 11·7-32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. Swiss National Science Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Toxicological Study No. 75-51-YJ81-93, 4-Amino-2-Nitrotoluene (4A2NT) Oral Approximate Lethal Dose 14-day Range Finding 90-Day Subchronic Feeding Studies in Rats, August 1991-November 1993

    DTIC Science & Technology

    1994-07-01

    NOVEMBER 1993 1. PURPOSE. The oral approximate lethal dose study was conducted todetennine an approximate dosage range at which to begin the 14-day...5000 mg/Kg. The 14-day range fmding study suggested a probable compound related effect in the薘~m (high dose ) exposure groups of both sexes and a...possible compound related effect mIlle 1000 ppm (middle dose ) exposure groups of both sexes. An NOAEL was not established for the 90-day subchronic

  7. Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis.

    PubMed

    Ashida, K; Sakurai, Y; Nishimura, A; Kudou, K; Hiramatsu, N; Umegaki, E; Iwakiri, K; Chiba, T

    2015-09-01

    The potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer clinical advantages over conventional therapy for acid-related disorders. To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO). In this multicentre, randomised, double-blind, parallel-group, dose-ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4. A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups. Vonoprazan was effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8-week study, while there was a dose-dependent increase in serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating EO. © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

  8. A Phase 2, Randomized, Controlled, Dose-Ranging Study Evaluating Crisaborole Topical Ointment, 0.5% and 2% in Adolescents With Mild to Moderate Atopic Dermatitis.

    PubMed

    Stein Gold, Linda F; Spelman, Lynda; Spellman, Mary C; Hughes, Matilda H; Zane, Lee T

    2015-12-01

    Crisaborole is a novel, boron-based, small-molecule, topical phosphodiesterase-4 inhibitor in development for the treatment of patients with mild to moderate atopic dermatitis (AD). In this multicenter, randomized, double-blind, dose-ranging, phase 2 study, adolescent patients 12 to 17 years of age with mild to moderate AD and 2 distinct target AD lesions were randomized to once-daily (QD) or twice-daily (BID) treatment with crisaborole topical ointment. For each patient, 2 target lesions were randomized to receive 29 days of treatment with 0.5% or 2% crisaborole topical ointment. The primary endpoint was change from baseline in AD severity index (ADSI) score for each lesion. Exploratory efficacy endpoints and safety were also assessed. A total of 86 patients were enrolled and received crisaborole topical ointment 0.5% or 2% QD (n=44) or BID (n=42). All dosing regimens produced dose-related improvements in ADSI as well as in all 5 component signs and symptoms of AD (erythema, excoriation, exudation, lichenification, and pruritus). The greatest improvements were consistently observed with crisaborole topical ointment, 2% applied BID. With this regimen, ADSI improved from baseline by 71%, and total or partial clearance of target lesions (ADSI ≤ 2) was achieved by 62% of patients after 29 days of treatment. Both doses of crisaborole topical ointment were well tolerated; mild application site reactions were the only treatment-related adverse events (QD, n=3; BID, n=1). These results provide preliminary evidence of the efficacy and safety of crisaborole topical ointment, 2% applied topically BID in adolescents with mild to moderate AD.

  9. Dosimetric comparison of extended dose range film with ionization measurements in water and lung equivalent heterogeneous media exposed to megavoltage photons.

    PubMed

    Charland, Paule M; Chetty, Indrin J; Yokoyama, Shigeru; Fraass, Benedick A

    2003-01-01

    In this study, a dosimetric evaluation of the new Kodak extended dose range (EDR) film versus ionization measurements has been conducted in homogeneous solid water and water-lung equivalent layered heterogeneous phantoms for a relevant range of field sizes (up to a field size of 25x25 cm2 and a depth of 15 cm) for 6 and 15 MV photon beams from a linear accelerator. The optical density of EDR film was found to be linear up to about 350 cGy and over-responded for larger fields and depths (5% for 25x25 cm2 at depth of 15 cm compared to a 10x10 cm2, 5 cm depth reference value). Central axis depth dose measurements in solid water with the film in a perpendicular orientation were within 2% of the Wellhöfer IC-10 measurements for the smaller field sizes. A maximum discrepancy of 8.4% and 3.9% was found for the 25x25 cm2 field at 15 cm depth for 6 and 15 MV photons, respectively (with curve normalization at a depth of 5 cm). Compared to IC-10 measurements, film measured central axis depth dose inside the lung slab showed a slight over-response (at most 2%). At a depth of 15 cm in the lung phantom the over-response was found to be 7.4% and 3.7% for the 25x25 cm2 field for 6 and 15 MV photons, respectively. When results were presented as correction factors, the discrepancy between the IC-10 and the EDR was greatest for the lowest energy and the largest field size. The effect of the finite size of the ion chamber was most evident at smaller field sizes where profile differences versus film were observed in the penumbral region. These differences were reduced at larger field sizes and in situations where lateral electron transport resulted in a lateral spread of the beam, such as inside lung material. Film profiles across a lung tumor geometry phantom agreed with the IC-10 chamber within the experimental uncertainties. From this investigation EDR film appears to be a useful medium for relative dosimetry in higher dose ranges in both water and lung equivalent material for

  10. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    PubMed

    van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

    2011-01-01

    Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

  11. Evaluation Of Microdosing Strategies For Studies In Preclinical Drug Development: Demonstration Of Linear Pharmacokinetics In Dogs Of A Nucleoside Analogue Over A 50-Fold Dose Range

    SciTech Connect

    Sandhu, P; Vogel, J S; Rose, M J; Ubick, E A; Brunner, J E; Wallace, M A; Adelsberger, J K; Baker, M P; Henderson, P T; Pearson, P G; Baillie, T A

    2004-04-22

    The technique of accelerator mass spectrometry (AMS) was validated successfully and utilized to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate (Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across sub-pharmacological (microdose) and pharmacological dose ranges in an animal model, prior to initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as LC-MS/MS and liquid scintillation counting analyses. Thus, Compound A displayed multiphasic kinetics and possessed low plasma clearance (4.4 mL/min/kg), a long terminal elimination half-life (19.4 hr) and high oral bioavailability (82%). Currently there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus sub-pharmacological doses employing microdosing strategies. The present study thus provides the first description of the pharmacokinetics of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A were similar following dosing at 0.02 mg/kg as at 1 mg/kg, indicating that in the case of Compound A, the kinetics of absorption, distribution and elimination in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even following a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques. The applications of accelerator mass spectrometry (AMS) are broad ranging and vary from studying environmental and ecological issues such as the isotopic composition of the atmosphere, soil and water (Hughen et al., 2000; Beck et al., 2001; Keith-Roach et al., 2001; Mironov et al., 2002), to archaeology and volcanology

  12. A dose-ranging study of pramipexole for the symptomatic treatment of restless legs syndrome: polysomnographic evaluation of periodic leg movements and sleep disturbance.

    PubMed

    Jama, Leni; Hirvonen, Kari; Partinen, Markku; Alakuijala, Anniina; Hublin, Christer; Tamminen, Ilkka; Koester, Juergen; Reess, Juergen

    2009-06-01

    To evaluate, both polysomnographically and by subjective scales, the efficacy and safety profile of pramipexole for restless legs syndrome (RLS) via a 3-week, double-blind, placebo-controlled, parallel-group, dose-ranging study. At baseline and after 3 weeks, periodic limb movements (PLM) and sleep parameters were assessed by polysomnography, and patients self-assessed their sleep disturbance and overall RLS severity using the international RLS study group rating scale (IRLS). Four pramipexole doses were evaluated: 0.125, 0.25, 0.50, and 0.75mg/d. Data from 107 patients were included in the intent-to-treat (ITT) analysis. For pramipexole recipients, the primary outcome measure, PLM per hour in bed asleep or awake (the PLM index, or PLMI), decreased by a median of -26.55 to -52.70 depending on dosage group, vs. -3.00 for placebo (p<0.01 or 0.001 for each group vs. placebo; Wilcoxon-Mann-Whitney test). Improvements in the secondary endpoints of PLM while asleep and while awake were also significantly superior for pramipexole. At 3 weeks, all pramipexole doses reduced the median for PLM while asleep to levels considered normal (<5PLM/h). Except for delta-sleep time and awakenings/arousals, sleep parameters remained unchanged or favored pramipexole. Median sleep latency was reduced by -5.00 to -11.75min in the pramipexole groups, vs. -2.00 for placebo (p<0.05 for all groups except 0.25mg/d). Median total sleep time increased by 25.75-66.75min, vs. 25.50 (p<0.05 for 0.50mg/d), and median time in stages 2-4/rapid eye movement (REM) sleep increased by 37.00-68.00min, vs. 26.75 (p<0.05 for 0.50mg/d). By subjective IRLS ratings, all pramipexole doses were significantly superior to placebo. Safety analysis demonstrated no dose-dependent increase in adverse events, and no drug-related increase in daytime somnolence was observed. Pramipexole is effective and well tolerated in RLS, most notably among objective measures, for reducing PLM and decreasing sleep latency. Although

  13. Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study

    PubMed Central

    Tebib, Jacques; Mariette, Xavier; Bourgeois, Pierre; Flipo, René-Marc; Gaudin, Philippe; Le Loët, Xavier; Gineste, Paul; Guy, Laurent; Mansfield, Colin D; Moussy, Alain; Dubreuil, Patrice; Hermine, Olivier; Sibilia, Jean

    2009-01-01

    Introduction Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. Methods This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. Results Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency

  14. A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems.

    PubMed

    Stocks, Jennifer Dugan; Taneja, Baldeo K; Baroldi, Paolo; Findling, Robert L

    2012-04-01

    To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder (ADHD) and serious conduct problems. This open-label, parallel-group, dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD and persistent, serious conduct problems to receive oral molindone thrice daily for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight <30 kg), group 2-20 mg (10 mg if <30 kg), group 3-30 mg (15 mg if <30 kg), and group 4-40 mg (20 mg if <30 kg). The primary outcome measure was to evaluate safety and tolerability of molindone in children with ADHD and serious conduct problems. Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale-revised (SNAP-IV) ADHD-related subscale scores. The study randomized 78 children; 55 completed the study. Treatment with molindone was generally well tolerated, with no clinically meaningful changes in laboratory or physical examination findings. The most common treatment-related adverse events (AEs) included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs increased with increasing dose. NCBRF-TIQ subscale scores improved in all four treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups 1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all treatment groups, and CGI-I scores improved to the greatest degree in group 4. Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20-40 mg (≥ 30 kg) was well tolerated, and preliminary

  15. Efficacy of a dose range of simulated sunlight exposures in raising vitamin D status in South Asian adults: implications for targeted guidance on sun exposure.

    PubMed

    Farrar, Mark D; Webb, Ann R; Kift, Richard; Durkin, Marie T; Allan, Donald; Herbert, Annie; Berry, Jacqueline L; Rhodes, Lesley E

    2013-06-01

    Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status. We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity. In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated. At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6 ng/mL; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL. Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the

  16. Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation.

    PubMed

    McCaffrey, Katherine A; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H; Patisaul, Heather B

    2013-05-01

    Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000μg/kg bw/day BPA through daily, non-invasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50mg/kg/day can alter sex specific hypothalamic morphology in the rat.

  17. Dose-Ranging Effects of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-On to Metformin in Subjects With Type 2 Diabetes

    PubMed Central

    Rosenstock, Julio; Aggarwal, Naresh; Polidori, David; Zhao, Yue; Arbit, Deborah; Usiskin, Keith; Capuano, George; Canovatchel, William

    2012-01-01

    OBJECTIVE To evaluate the effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes mellitus inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS This was a double-blind, placebo-controlled, parallel-group, multicenter, dose-ranging study in 451 subjects randomized to canagliflozin 50, 100, 200, or 300 mg once daily (QD) or 300 mg twice daily (BID), sitagliptin 100 mg QD, or placebo. Primary end point was change in A1C from baseline through week 12. Secondary end points included change in fasting plasma glucose (FPG), body weight, and overnight urinary glucose-to-creatinine ratio. Safety and tolerability were also assessed. RESULTS Canagliflozin was associated with significant reductions in A1C from baseline (7.6–8.0%) to week 12: −0.79, −0.76, −0.70, −0.92, and −0.95% for canagliflozin 50, 100, 200, 300 mg QD and 300 mg BID, respectively, versus −0.22% for placebo (all P < 0.001) and −0.74% for sitagliptin. FPG was reduced by −16 to −27 mg/dL, and body weight was reduced by −2.3 to −3.4%, with significant increases in urinary glucose-to-creatinine ratio. Adverse events were transient, mild to moderate, and balanced across arms except for a non–dose-dependent increase in symptomatic genital infections with canagliflozin (3–8%) versus placebo and sitagliptin (2%). Urinary tract infections were reported without dose dependency in 3–9% of canagliflozin, 6% of placebo, and 2% of sitagliptin arms. Overall incidence of hypoglycemia was low. CONCLUSIONS Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss. The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females. PMID:22492586

  18. Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation

    PubMed Central

    McCaffrey, Katherine A.; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H.; Patisaul, Heather B.

    2013-01-01

    Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000 mg/kg bw/day BPA through daily, noninvasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50 mg/kg/day can alter sex specific hypothalamic morphology in the rat. PMID:23500335

  19. Longitudinal studies of cardiac troponin-I concentrations in serum from male Sprague Dawley rats: baseline reference ranges and effects of handling and placebo dosing on biological variability.

    PubMed

    Schultze, A Eric; Carpenter, Kent H; Wians, Frank H; Agee, Sara J; Minyard, Jennifer; Lu, Quynh Anh; Todd, John; Konrad, Robert J

    2009-10-01

    Serum cardiac troponin-I has been validated as a biomarker for cardiotoxicity in numerous animal models; however, baseline reference ranges for cTnI concentration in a healthy population of laboratory rats, as well as an investigation of biological cTnI variability in rats with respect to time, handling, and placebo dosing methods, have not been reported. In this study, we used an ultrasensitive cTnI immunoassay to quantify hourly concentrations of cTnI in live rats handled under standard laboratory conditions using 15 microL of serum per determination. The baseline reference range (mean 4.94 pg/mL, range 1-15 pg/mL, 99% confidence interval [CI]) of cTnI concentration in rats was consistent with previously reported reference ranges for cTnI in humans (1-12 pg/mL) and with preliminary studies in dogs (1-4 pg/mL) and monkeys (4-5 pg/mL) using the same cTnI assay method. In addition, cTnI concentrations in individual rat serum samples show minimal biological variability over a twenty-four-hour interval when compared to a meaningful reference change value of 193% to 206%. Furthermore, measurements of cTnI concentration were consistent within the reference limits in individual rats over long periods and under three different standard laboratory handling conditions. Thus, using this new method, rats can be followed longitudinally at hourly intervals, and a doubling of cTnI concentration would be significant above biological variability. This is a new paradigm for preclinical testing, which allows transient changes in cTnI concentration to be accurately quantified. This understanding of baseline and biological variability in rats will be fundamental for designing and analyzing future studies that assess potential cardiotoxicity in drug development.

  20. Reduction of the unnecessary dose from the over-range area with a spiral dynamic z-collimator: comparison of beam pitch and detector coverage with 128-detector row CT.

    PubMed

    Shirasaka, Takashi; Funama, Yoshinori; Hayashi, Mutsukazu; Awamoto, Shinichi; Kondo, Masatoshi; Nakamura, Yasuhiko; Hatakenaka, Masamitsu; Honda, Hiroshi

    2012-01-01

    Our purpose in this study was to assess the radiation dose reduction and the actual exposed scan length of over-range areas using a spiral dynamic z-collimator at different beam pitches and detector coverage. Using glass rod dosimeters, we measured the unilateral over-range scan dose between the beginning of the planned scan range and the beginning of the actual exposed scan range. Scanning was performed at detector coverage of 80.0 and 40.0 mm, with and without the spiral dynamic z-collimator. The dose-saving ratio was calculated as the ratio of the unnecessary over-range dose, with and without the spiral dynamic z-collimator. In 80.0 mm detector coverage without the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 108, 120, and 126 mm, corresponding to a beam pitch of 0.60, 0.80, and 0.99, respectively. With the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 48, 66, and 84 mm with a beam pitch of 0.60, 0.80, and 0.99, respectively. The dose-saving ratios with and without the spiral dynamic z-collimator for a beam pitch of 0.60, 0.80, and 0.99 were 35.07, 24.76, and 13.51%, respectively. With 40.0 mm detector coverage, the dose-saving ratios with and without the spiral dynamic z-collimator had the highest value of 27.23% with a low beam pitch of 0.60. The spiral dynamic z-collimator is important for a reduction in the unnecessary over-range dose and makes it possible to reduce the unnecessary dose by means of a lower beam pitch.

  1. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies.

    PubMed

    Buse, John B; DeFronzo, Ralph A; Rosenstock, Julio; Kim, Terri; Burns, Colleen; Skare, Sharon; Baron, Alain; Fineman, Mark

    2016-02-01

    Delayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediate-release metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. Study 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). The bioavailability of 1,000 mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. 7 CFR 3.20 - Standards for suspending or terminating collection activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... activities. 3.20 Section 3.20 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Standards for the Administrative Collection and Compromise of Claims § 3.20 Standards for suspending or terminating collection activities. An agency shall follow the standards set forth in 31 CFR part 903 for the...

  3. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study.

    PubMed

    Held, Jana; Supan, Christian; Salazar, Carmen L O; Tinto, Halidou; Bonkian, Léa N; Nahum, Alain; Moulero, Bancole; Sié, Ali; Coulibaly, Boubacar; Sirima, Sodiomon B; Siribie, Mohamadou; Otsyula, Nekoye; Otieno, Lucas; Abdallah, Ahmed M; Kimutai, Robert; Bouyou-Akotet, Marielle; Kombila, Maryvonne; Koiwai, Kimiko; Cantalloube, Cathy; Din-Bell, Chantal; Djeriou, Elhadj; Waitumbi, John; Mordmüller, Benjamin; Ter-Minassian, Daniel; Lell, Bertrand; Kremsner, Peter G

    2015-12-01

    Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. Ferroquine is a new combination partner for fast-acting ACTs such as artesunate. We aimed to assess different doses of ferroquine in combination with artesunate against uncomplicated P falciparum malaria in a heterogeneous population in Africa. We did a phase 2, multicentre, parallel-group, double-blind, randomised, dose-ranging non-inferiority trial at eight African hospitals (two in Gabon, three in Burkina Faso, one in Benin, and two in Kenya). We recruited patients presenting with acute P falciparum monoinfection (1000-200,000 parasites per μL), and a central body temperature of at least 37·5°C or history of fever in the past 24 h. We assessed patients in two sequential cohorts: cohort 1 contained adults (bodyweight >50 kg) and adolescents (aged ≥14 years, >30 kg), and cohort 2 contained children (aged 2-13 years, 15-30 kg). We randomly assigned patients (1:1:1:1) to receive artesunate 4 mg/kg per day plus ferroquine 2 mg/kg, 4 mg/kg, or 6 mg/kg, given double-blind once per day for 3 days, or ferroquine monotherapy 4 mg/kg per day given single-blind (ie, allocation was only masked from the patient) once per day for 3 days. We did 14 patient visits (screening, 3 treatment days and 48 h post-treatment surveillance, a visit on day 7, then one follow-up visit per week until day 63). The primary endpoint was non-inferiority of treatment in terms of PCR-corrected cure rate against a reference value of 90%, with a 10% non-inferiority margin, assessed in patients treated without major protocol deviations for parasitologically confirmed malaria. We assessed safety in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00988507, and is closed. Between Oct 16, 2009, and Sept 22, 2010, we randomly assigned 326 eligible patients to treatment groups, with last follow-up visit on Dec 1, 2010. 284 patients

  4. Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study.

    PubMed

    Galea, James; Ogungbenro, Kayode; Hulme, Sharon; Greenhalgh, Andrew; Aarons, Leon; Scarth, Sylvia; Hutchinson, Peter; Grainger, Samantha; King, Andrew; Hopkins, Stephen J; Rothwell, Nancy; Tyrrell, Pippa

    2011-02-01

    The naturally occurring antagonist of interleukin-1, IL-1RA, is highly neuroprotective experimentally, shows few adverse effects, and inhibits the systemic acute phase response to stroke. A single regime pilot study showed slow penetration into cerebrospinal fluid (CSF) at experimentally therapeutic concentrations. Twenty-five patients with subarachnoid hemorrhage (SAH) and external ventricular drains were sequentially allocated to five administration regimes, using intravenous bolus doses of 100 to 500 mg and 4 hours intravenous infusions of IL-1RA ranging from 1 to 10 mg per kg per hour. Choice of regimes and timing of plasma and CSF sampling was informed by pharmacometric analysis of pilot study data. Data were analyzed using nonlinear mixed effects modeling. Plasma and CSF concentrations of IL-1RA in all regimes were within the predicted intervals. A 500-mg bolus followed by an intravenous infusion of IL-1RA at 10 mg per kg per hour achieved experimentally therapeutic CSF concentrations of IL-1RA within 45 minutes. Experimentally, neuroprotective CSF concentrations in patients with SAH can be safely achieved within a therapeutic time window. Pharmacokinetic analysis suggests that IL-1RA transport across the blood-CSF barrier in SAH is passive. Identification of the practicality of this delivery regime allows further studies of efficacy of IL-1RA in acute cerebrovascular disease.

  5. Dose ranging of adjuvant and antigen in a cell culture H5N1 influenza vaccine: safety and immunogenicity of a phase 1/2 clinical trial.

    PubMed

    Keitel, Wendy; Groth, Nicola; Lattanzi, Maria; Praus, Michaela; Hilbert, Anne Katrin; Borkowski, Astrid; Tsai, Ted F

    2010-01-08

    Dose-sparing strategies and new production technologies will be necessary to produce adequate supplies of vaccines for pandemic influenza. One approach is to include adjuvant, which can reduce the amount of antigen required for immunization and stimulate cross-reactive responses to drifted variants of novel viruses. Dose-sparing studies of adjuvant, itself a finite resource, have not previously been reported for H5N1 vaccine development. A total of 753 healthy 18-40-year-old adults were randomized to one of 12 groups (N approximately 60/group) to receive two intramuscular doses, 21 days apart, of 3.75, 7.5 or 15 microg of cell culture grown influenza A/H5N1 hemagglutinin (A/Indonesia/5/2005 (H5N1)/PR-8-IBCDC-RG2), each dose level formulated with 0%, 25%, 50% or 100% of the MF59 dose contained in licensed influenza vaccine. 752 subjects actually received one dose, and 695 a second dose. Serum hemagglutination inhibition and neutralizing antibody levels, were determined before and 21 days after each dose. Safety and reactogenicity were assessed by self-completed diary cards. Nonadjuvanted H5N1 formulations were poorly immunogenic, but antibody responses were significantly enhanced by all doses of MF59 for each antigen level. The 3.75 microg H5N1 containing 50% MF59 satisfied the European criteria for pandemic vaccine licensure. All formulations were well tolerated, although MF59 dose-dependent increases in the frequency of injection site pain were observed. The frequencies of injection site and systemic reactions were lower after receipt of the second dose of vaccine. No vaccine-related SAE was reported. Dose-sparing of both antigen and adjuvant is possible without compromising immunogenicity, while improving reactogenicity and is a promising strategy that will expand the availability of vaccines for global control of pandemic influenza.

  6. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony).

    PubMed

    Abrams, Paul; Kelleher, Con; Staskin, David; Rechberger, Tomasz; Kay, Richard; Martina, Reynaldo; Newgreen, Donald; Paireddy, Asha; van Maanen, Rob; Ridder, Arwin

    2015-03-01

    Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic (AM) agent solifenacin may improve efficacy in the treatment of overactive bladder (OAB) while reducing the AM side effects. The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5mg monotherapy. The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy. A phase 2, factorial design, randomised, double-blind, parallel-group, placebo- and monotherapy-controlled trial, conducted at 141 sites in 20 European countries. Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo. A total of 1306 patients (66.4% female) were randomised to 12 wk of treatment in 1 of 12 groups: 6 combination groups (solifenacin 2.5, 5, or 10 mg plus mirabegron 25 or 50 mg), 5 monotherapy groups (solifenacin 2.5, 5, or 10 mg, or mirabegron 25 or 50 mg), or placebo. Change from baseline to end of treatment in mean volume voided per micturition (MVV) (primary end point) and mean numbers of micturitions per 24 h, incontinence episodes per 24 h, and urgency episodes per 24 h were analysed using an analysis of covariance model. Safety assessments included treatment-emergent adverse events (TEAEs), blood pressure, pulse rate, postvoid residual (PVR) volume, and laboratory and electrocardiography (ECG) parameters. Compared with solifenacin 5 mg monotherapy, all combinations with solifenacin 5 or 10 mg significantly improved MVV, with adjusted differences ranging from 18.0 ml (95% confidence interval [CI], 5.4-30.0) to 26.3 ml (95% CI, 12.0-41.0). Three combination groups significantly reduced micturition frequency compared with solifenacin 5 mg, ranging from -0.80 (95% CI, -1.39 to -0.22) to -0.98 (95% CI, -1.68 to -0.27). Five of six combinations significantly reduced urgency episodes compared with solifenacin 5 mg, ranging from -0.98 (95% CI, -1.78, to -0.18) to -1

  7. [An evaluation of the biological action of increased doses of EMI in the UV range on the functional state and productivity of sheep].

    PubMed

    Ivanov, V L; Ipatova, A G; Zeĭnalov, A A; Kozlov, V A; Sarukhanov, V Ia

    2000-01-01

    The effect of increased UV-radiation doses modeling 25 and 50% of ozone layer depletion on sheep's organisms was studied in the field experiment. The character of changes in animal organisms was found to depend on irradiation doses, sensitivity of individual system of living organism to electromagnetic radiation and physiological peculiarities of protection.

  8. A dose-ranging study of a subunit Respiratory Syncytial Virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age.

    PubMed

    Langley, Joanne M; Sales, Valerie; McGeer, Allison; Guasparini, Roland; Predy, Gerald; Meekison, William; Li, Minran; Capellan, Jose; Wang, Elaine

    2009-09-25

    We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.

  9. Effects of single shot femoral nerve block combined with intrathecal morphine for postoperative analgesia: a randomized, controlled, dose-ranging study after total knee arthroplasty.

    PubMed

    Kunopart, Mutita; Chanthong, Pratamaporn; Thongpolswat, Nimit; Intiyanaravut, Tawan; Pethuahong, Chanyapat

    2014-02-01

    Pain after total knee arthroplasty (TKA) is severe, thus adequate pain control can be a challenge. Intrathecal morphine (ITM) provides excellent postoperative analgesia for TKA, but may have side effects. Femoral nerve block (FNB) also has been used for postoperative analgesia in TKA. We examined postoperative analgesia efficacy and side effects of ITM combined with single shot femoral nerve block (SSFNB) after TKA, over the dosage range of 0.0 to 0.3 mg. Sixty patients undergoing elective TKA received SSFNB (0.5% bupivacaine 20 ml) and spinal anesthesia with 15 mg of hyperbaric bupivacaine (0.5% Heavy Marcaine) were included in this study. They were randomized to receive ITM (0, 0.1, 0.2, and 0.3 mg). A patient-controlled analgesia (PCA) device provided additional intravenous morphine. Morphine consumption, pain score, and side effects were recorded at 0, 1, 4, 8, 12, and 24 hour postoperative. Patient satisfaction was rated at the 24-hour postoperative visit. Morphine consumption was significant higher in 0 mg ITM group (control) than other groups, but there was no difference between ITM groups. Pain score was significant lower in 0.3 mg ITM group compared to 0 mg at 1 hour (0.5 vs. 3.5, respectively; p-value = 0.013) and 4 hour (1.5 vs. 4.5, respectively; p-value = 0.037) postoperative period Side effects were not different in all groups. The present study concluded that, low-dose ITM combination with SSFNB provided good pain relief with low side effects and reduced morphine consumption during the first 24 hours post TKA.

  10. Emotional impact of genetic trials in progressive paediatric disorders: a dose-ranging exon-skipping trial in Duchenne muscular dystrophy.

    PubMed

    Garralda, M E; McConachie, H; Le Couteur, A; Sriranjan, S; Chakrabarti, I; Cirak, S; Guglieri, M; Bushby, K; Muntoni, F

    2013-05-01

    Gene-modifying trials offer hope for improvement in chronic paediatric disorders, but they may also lead to disappointment and have an adverse emotional effect on families. This study aimed to examine emotional impact on participants in a paediatric exon-skipping trial. Nineteen male children with Duchenne muscular dystrophy (DMD), and their parents, taking part in a dose-ranging study of an i.v. administered morpholino splice-switching oligomer (which can restore the reading frame in DMD and induce dystrophin expression) underwent a psychosocial/psychiatric examination at trial entry. Emotional impact was assessed at trial completion using questionnaires. The mean child age was 8.9 years (SD 2.1); 13(68%) were attending mainstream school. Most families were well adjusted psychosocially at trial entry. Post-trial median child emotional impact scores were 5/10 (n= 18), but impact was rated as positive by 6/14 (42%), neutral/mixed by 5 (35%) and negative by 3 (21%). Median post-trial psychosocial/psychiatric change scores in children and parents were minimal. Actual post-trial negative impact was statistically significantly associated with higher expected impact at trial entry, at which time the families of the three children displaying actual negative impact reported higher family stress levels in combination with a variety of other psychosocial risks factors. In carefully selected families with low levels of psychosocial stress/distress at trial entry, and with good support from paediatric research units (including psychiatric input when required), genetic trials in progressive disorders such as DMD can have a predominantly positive or neutral emotional impact. Nevertheless, negative impact is reported by a minority of families and possible psychosocial predictors deserving further scrutiny have been identified. © 2012 Blackwell Publishing Ltd.

  11. Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa)

    PubMed Central

    Connolly, Stuart J.; Eikelboom, John; Dorian, Paul; Hohnloser, Stefan H.; Gretler, Daniel D.; Sinha, Uma; Ezekowitz, Michael D.

    2013-01-01

    Aims Patients with atrial fibrillation (AF) are at increased risk of stroke. Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly excreted unchanged in the bile and with low (17%) renal excretion. Methods and results Patients with AF and more than one risk factor for stroke were randomized to one of three blinded doses of betrixaban (40, 60, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0–3.0. The primary outcome was major or clinically relevant non-major bleeding. The mean follow-up was 147 days. Among 508 patients randomized, the mean CHADS2 score was 2.2; 87% of patients had previously received vitamin K antagonist therapy. The time in therapeutic range on warfarin was 63.4%. There were one, five, five, and seven patients with a primary outcome on betrixaban 40, 60, 80 mg daily, or warfarin, respectively. The rate of the primary outcome was lowest on betrixaban 40 mg (hazard ratio compared with warfarin = 0.14, exact stratified log-rank P-value 0.04, unadjusted for multiple testing). Rates of the primary outcome with betrixaban 60 or 80 mg were more similar to those of wafarin. Two ischaemic strokes occurred, one each on betrixaban 60 and 80 mg daily. There were two vascular deaths, one each on betrixaban 40 mg and warfarin. Betrixaban was associated with higher rates of diarrhoea than warfarin. Conclusion Betrixaban was well tolerated and had similar or lower rates of bleeding compared with well-controlled warfarin in patients with AF at risk for stroke. PMID:23487517

  12. A Phase 1 dose-ranging study examining the effects of a superabsorbent polymer (CLP) on fluid, sodium and potassium excretion in healthy subjects

    PubMed Central

    2014-01-01

    Background CLP is an orally administered, non-absorbed, superabsorbent polymer being developed to increase fecal excretion of sodium, potassium and water in patients with heart failure and end-stage renal disease. This study was conducted to evaluate the safety of CLP, and to explore dose-related effects on fecal weight, fecal and urine sodium and potassium excretion, and serum electrolyte concentrations. Methods This Phase 1, open-label, dose-escalation study included 25 healthy volunteers, who were administered CLP orally immediately prior to four daily meals for 9 days at doses of 7.5, 15.0, and 25.0 g/day (n = 5/group). An additional dose group received 15.0 g/day CLP under fasting conditions, and an untreated cohort (n = 5) served as control. Twenty-four-hour fecal and urinary output was collected daily. Samples were weighed, and sodium, potassium, and other ion content in stool and urine were measured for each treatment group. Effects on serum cation concentrations, other standard laboratory values, and adverse events were also determined. Results At doses below 25.0 g/day, CLP was well tolerated, with a low frequency of self-limiting gastrointestinal adverse events. CLP increased fecal weight and fecal sodium and potassium content in a dose-related manner. Concomitant dose-related decreases in urinary sodium and potassium were observed. All serum ion concentrations remained within normal limits. Conclusions In this study, oral CLP removed water, sodium and potassium from the body via the gastrointestinal tract in a dose related fashion. CLP could become useful for patients with fluid overload and compromised kidney function in conditions such as congestive heart failure, salt sensitive hypertension, chronic kidney disease and end stage renal disease. Trial registration NCT01944007 PMID:24460668

  13. Randomized dose-ranging study of the 14-day early bactericidal activity of bedaquiline (TMC207) in patients with sputum microscopy smear-positive pulmonary tuberculosis.

    PubMed

    Diacon, Andreas H; Dawson, Rodney; Von Groote-Bidlingmaier, Florian; Symons, Gregory; Venter, Amour; Donald, Peter R; Conradie, Almari; Erondu, Ngozi; Ginsberg, Ann M; Egizi, Erica; Winter, Helen; Becker, Piet; Mendel, Carl M

    2013-05-01

    Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies.

  14. A photobleaching-based PDT dose metric predicts PDT efficacy over certain BPD concentration ranges in a three-dimensional model of ovarian cancer

    NASA Astrophysics Data System (ADS)

    Anbil, S.; Rizvi, I.; Celli, J. P.; Alagic, N.; Hasan, T.

    2013-03-01

    Photodynamic therapy (PDT) dosimetry is an active area of study that is motivated by the need to reliably predict treatment outcomes. Implicit dosimetric parameters, such as photosensitizer (PS) photobleaching, may indicate PDT efficacy and could establish a framework to provide patient-customized PDT. Here, tumor destruction and benzoporphryin-derivative (BPD) photobleaching are characterized by systematically varying BPD-light combinations to achieve fixed PDT doses (M * J * cm-2) in a three-dimensional (3D) model of micrometastatic ovarian cancer (OvCa). It is observed that the BPD-light parameters used to construct a given PDT dose significantly impact nodule viability and BPD photobleaching. As a result, PDT dose, when measured by the product of BPD concentration and fluence, does not reliably predict overall efficacy. A PDT dose metric that incorporates a term for BPD photobleaching more robustly predicts PDT efficacy at low concentrations of BPD. These results suggest that PDT dose metrics that are informed by implicit approaches to dosimetry could improve the reliability of PDT-based regimens and provide opportunities for patient-specific treatment planning.

  15. 38 CFR 3.20 - Surviving spouse's benefit for month of veteran's death.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... after December 1, 1962, and before October 1, 1982, the rate of death pension or dependency and... or after October 1, 1982, the surviving spouse may be paid death pension or dependency and indemnity... benefit for month of veteran's death. 3.20 Section 3.20 Pensions, Bonuses, and Veterans' Relief...

  16. 38 CFR 3.20 - Surviving spouse's benefit for month of veteran's death.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... after December 1, 1962, and before October 1, 1982, the rate of death pension or dependency and... or after October 1, 1982, the surviving spouse may be paid death pension or dependency and indemnity... benefit for month of veteran's death. 3.20 Section 3.20 Pensions, Bonuses, and Veterans' Relief...

  17. 38 CFR 3.20 - Surviving spouse's benefit for month of veteran's death.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... after December 1, 1962, and before October 1, 1982, the rate of death pension or dependency and... or after October 1, 1982, the surviving spouse may be paid death pension or dependency and indemnity... benefit for month of veteran's death. 3.20 Section 3.20 Pensions, Bonuses, and Veterans' Relief...

  18. 38 CFR 3.20 - Surviving spouse's benefit for month of veteran's death.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... after December 1, 1962, and before October 1, 1982, the rate of death pension or dependency and... or after October 1, 1982, the surviving spouse may be paid death pension or dependency and indemnity... benefit for month of veteran's death. 3.20 Section 3.20 Pensions, Bonuses, and Veterans' Relief...

  19. 38 CFR 3.20 - Surviving spouse's benefit for month of veteran's death.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... after December 1, 1962, and before October 1, 1982, the rate of death pension or dependency and... or after October 1, 1982, the surviving spouse may be paid death pension or dependency and indemnity... benefit for month of veteran's death. 3.20 Section 3.20 Pensions, Bonuses, and Veterans' Relief...

  20. Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.

    PubMed

    Walsh, D S; Looareesuwan, S; Wilairatana, P; Heppner, D G; Tang, D B; Brewer, T G; Chokejindachai, W; Viriyavejakul, P; Kyle, D E; Milhous, W K; Schuster, B G; Horton, J; Braitman, D J; Brueckner, R P

    1999-10-01

    WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

  1. Comparison of peripheral and central effects of single and repeated oral dose administrations of bilastine, a new H1 antihistamine: a dose-range study in healthy volunteers with hydroxyzine and placebo as control treatments.

    PubMed

    García-Gea, Consuelo; Martínez-Colomer, Joan; Antonijoan, Rosa M; Valiente, Román; Barbanoj, Manuel-José

    2008-12-01

    Peripheral anti-H1 and central nervous system (CNS) activities after single (day 1) and repeated (day 7) administrations of increasing doses of bilastine (BIL) were assessed in 20 healthy volunteers throughout a crossover, randomized, double-blind, placebo (PLA)-controlled study. Repeated doses of BIL 20, 40, or 80 mg and hydroxyzine 25 mg (HYD) as positive standard were administered on 7 consecutive days. Before and at several time points after drug intake, skin reactivity to the intradermal injection of histamine, objective tests of psychomotor performance, and subjective mood scales were evaluated. All active treatments led to a significant and similar reduction in the wheal reaction in relation to PLA after both the single (P < 0.001) and repeated administrations (P < 0.001). No delay was observed in the onset of its peripheral activity after the first dose of BIL as compared with HYD. No tolerance or sensitization was seen when comparing acute and repetitive assessments. Central nervous system effects showed that HYD induced the greatest psychomotor impairment (P < 0.05). Repeated HYD intake showed a lower number of significant alterations in comparison to acute administration. Bilastine 80 mg also showed some impairment (P < 0.05). Subjectively, the only active treatment that could not be differentiated from PLA was BIL 20 mg. Hydroxyzine 25 mg showed the greatest differentiation (P < 0.01). A clear dissociation between peripheral anti-H1 and CNS activity was found after BIL treatment. Significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL. The 40-mg dose of BIL produced subjective report of sedation, whereas unwanted objective CNS side effects were observed only with the 80-mg dose.

  2. A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia

    PubMed Central

    Mahoney, Erin; Jackson, Saheeda; Hutzelmann, Jill; Zhao, Xin; Jia, Nan; Snyder, Ellen; Snavely, Duane; Michelson, David; Roth, Thomas; Herring, W. Joseph

    2016-01-01

    Background: Filorexant (MK-6096) is an orexin receptor antagonist; here, we evaluate the efficacy of filorexant in the treatment of insomnia in adults. Methods: A double-blind, placebo-controlled, randomized, two 4-week–period, adaptive crossover polysomnography study was conducted at 51 sites worldwide. Patients (18 to <65 years) with insomnia received 1 of 4 doses of oral filorexant (2.5, 5, 10, 20mg) once daily at bedtime during one period and matching placebo in the other period in 1 of 8 possible treatment sequences. Polysomnography was performed on night 1 and end of week 4 of each period. The primary endpoint was sleep efficiency at night 1 and end of week 4. Secondary endpoints included wakefulness after persistent sleep onset and latency to onset of persistent sleep. Results: A total of 324 patients received study treatment, 315 received ≥1 dose of placebo, and 318 ≥1 dose of filorexant (2.5mg, n=79; 5mg, n=78; 10mg, n=80; 20mg, n=81). All filorexant doses (2.5/5/10/20mg) were significantly superior to placebo in improving sleep among patients with insomnia as measured by sleep efficiency and wakefulness after persistent sleep onset on night 1 and end of week 4. The 2 higher filorexant doses (10/20mg) were also significantly more effective than placebo in improving sleep onset as measured by latency to onset of persistent sleep at night 1 and end of week 4. Filorexant was generally well tolerated. Conclusions: Orexin receptor antagonism by filorexant significantly improved sleep efficiency in nonelderly patients with insomnia. Dose-related improvements in sleep onset and maintenance outcomes were also observed with filorexant. PMID:26979830

  3. Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude

    PubMed Central

    Gerhold, Katharina J.; Drdla-Schutting, Ruth; Honsek, Silke D.; Forsthuber, Liesbeth

    2015-01-01

    Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C-fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 μg·kg−1, buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively μ1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective μ1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 μg·kg−1), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive μ-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct μ-opioid receptor subtypes located at different levels of the neuraxis. PMID:26134641

  4. A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis.

    PubMed

    Halse, Johan; Greenspan, Susan; Cosman, Felicia; Ellis, Graham; Santora, Arthur; Leung, Albert; Heyden, Norman; Samanta, Suvajit; Doleckyj, Steven; Rosenberg, Elizabeth; Denker, Andrew E

    2014-11-01

    MK-5442 is an orally bioavailable calcium-sensing receptor antagonist that is hypothesized to stimulate bone formation by stimulating endogenous secretion of a pulse of PTH. Earlier clinical and preclinical studies demonstrated increased bone mineral density (BMD) after treatment. Our objective was to identify a dose of MK-5442 that produces osteoanabolic effects without excessive hypercalcemia. This was a randomized, double-blind, placebo-controlled, parallel-group trial of private or institutional practice. In total, 383 postmenopausal women with osteoporosis were administered daily oral MK-5442 (2.5, 5, 7.5, 10, or 15 mg) or placebo. Serum PTH and calcium, bone turnover markers, areal BMD, and safety were evaluated. A dose-dependent transient increase in PTH occurred after an MK-5442 dose and lasted more than 3.5 hours. Compared with placebo, significant increases in bone formation markers (serum procollagen 1 N-terminal peptide and bone-specific alkaline phosphatase) were observed by 6 months, whereas bone resorption markers (serum C-telopeptide of type 1 collagen, urine N-telopeptides of type 1 collagen) initially decreased but were also significantly increased by 6 months. Despite the biochemical marker changes suggestive of an anabolic response, there were no statistically significant differences between any dose of MK-5442 and placebo in percent change from baseline at month 6 in any of the BMD endpoints. The frequency of hypercalcemia (trough serum calcium ≥ 10.8 mg/dL) was greater with higher MK-5442 doses. In postmenopausal women with low bone mass, treatment with MK-5442 resulted in transient pulses of PTH. Bone formation markers increased quickly and bone resorption markers decreased temporarily, suggestive of an anabolic window. However, there were no increases in BMD versus placebo.

  5. A Phase 2, Randomized, Placebo-Controlled, Dose-Ranging Study of the Calcium-Sensing Receptor Antagonist MK-5442 in the Treatment of Postmenopausal Women With Osteoporosis

    PubMed Central

    Greenspan, Susan; Cosman, Felicia; Ellis, Graham; Santora, Arthur; Leung, Albert; Heyden, Norman; Samanta, Suvajit; Doleckyj, Steven; Rosenberg, Elizabeth; Denker, Andrew E.

    2014-01-01

    Context: MK-5442 is an orally bioavailable calcium-sensing receptor antagonist that is hypothesized to stimulate bone formation by stimulating endogenous secretion of a pulse of PTH. Earlier clinical and preclinical studies demonstrated increased bone mineral density (BMD) after treatment. Objective: Our objective was to identify a dose of MK-5442 that produces osteoanabolic effects without excessive hypercalcemia. Design and Setting: This was a randomized, double-blind, placebo-controlled, parallel-group trial of private or institutional practice. Participants and Intervention: In total, 383 postmenopausal women with osteoporosis were administered daily oral MK-5442 (2.5, 5, 7.5, 10, or 15 mg) or placebo. Main Outcome Measures: Serum PTH and calcium, bone turnover markers, areal BMD, and safety were evaluated. Results: A dose-dependent transient increase in PTH occurred after an MK-5442 dose and lasted more than 3.5 hours. Compared with placebo, significant increases in bone formation markers (serum procollagen 1 N-terminal peptide and bone-specific alkaline phosphatase) were observed by 6 months, whereas bone resorption markers (serum C-telopeptide of type 1 collagen, urine N-telopeptides of type 1 collagen) initially decreased but were also significantly increased by 6 months. Despite the biochemical marker changes suggestive of an anabolic response, there were no statistically significant differences between any dose of MK-5442 and placebo in percent change from baseline at month 6 in any of the BMD endpoints. The frequency of hypercalcemia (trough serum calcium ≥10.8 mg/dL) was greater with higher MK-5442 doses. Conclusion: In postmenopausal women with low bone mass, treatment with MK-5442 resulted in transient pulses of PTH. Bone formation markers increased quickly and bone resorption markers decreased temporarily, suggestive of an anabolic window. However, there were no increases in BMD versus placebo. PMID:25166719

  6. Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients: Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age Range.

    PubMed

    Hanley, Michael J; Mould, Diane R; Taylor, Timothy J; Gupta, Neeraj; Suryanarayan, Kaveri; Neuwirth, Rachel; Esseltine, Dixie-Lee; Horton, Terzah M; Aplenc, Richard; Alonzo, Todd A; Lu, Xiaomin; Milton, Ashley; Venkatakrishnan, Karthik

    2017-09-01

    This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1.3 mg/m(2) twice-weekly, on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11 of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood samples were obtained and the plasma was harvested on day 8 over 0-72 hours postdose to measure bortezomib concentrations by liquid chromatography-tandem mass spectrometry. Concentration-time data were analyzed by nonlinear mixed-effects modeling. Covariates were examined using forward addition (P < .01)/backward elimination (P < .001). Data were included from 104 patients (49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2-11 years/12-16 years). Bortezomib pharmacokinetics were described by a 3-compartment model with linear elimination. Body surface area adequately accounted for variability in clearance (exponent 0.97), supporting body surface area-based dosing. Stratified visual predictive check simulations verified that neither age group nor patient population represented sources of meaningful pharmacokinetic heterogeneity not accounted for by the final population pharmacokinetic model. Following administration of 1.3 mg/m(2) intravenous bortezomib doses, body surface area-normalized clearance in pediatric patients was similar to that observed in adult patients, thereby indicating that this dose achieves similar systemic exposures in pediatric patients. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley

  7. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

    PubMed

    Viney, Nicholas J; van Capelleveen, Julian C; Geary, Richard S; Xia, Shuting; Tami, Joseph A; Yu, Rosie Z; Marcovina, Santica M; Hughes, Steven G; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T; Witztum, Joseph L; Stroes, Erik S; Tsimikas, Sotirios

    2016-11-05

    Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. We did two randomised, double-blind, placebo-controlled trials. In a phase 2 trial (done in 13 study centres in Canada, the Netherlands, Germany, Denmark, and the UK), we assessed the effect of IONIS-APO(a)Rx, an oligonucleotide targeting apolipoprotein(a). Participants with elevated Lp(a) concentrations (125-437 nmol/L in cohort A; ≥438 nmol/L in cohort B) were randomly assigned (in a 1:1 ratio in cohort A and in a 4:1 ratio in cohort B) with an interactive response system to escalating-dose subcutaneous IONIS-APO(a)Rx (100 mg, 200 mg, and then 300 mg, once a week for 4 weeks each) or injections of saline placebo, once a week, for 12 weeks. Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration at day 85 or 99 in the per-protocol population (participants who received more than six doses of study drug) and safety and tolerability in the safety population. In a phase 1/2a first-in-man trial, we assessed the effect of IONIS-APO(a)-LRx, a ligand-conjugated antisense oligonucleotide designed to be highly and selectively taken up by hepatocytes, at the BioPharma Services phase 1 unit (Toronto, ON, Canada). Healthy volunteers (Lp[a] ≥75 nmol/L) were randomly assigned to receive a single dose of 10-120 mg IONIS-APO(a)LRx subcutaneously in an ascending-dose design or placebo (in a 3:1 ratio; single-ascending-dose phase), or multiple doses of 10 mg, 20 mg, or 40 mg IONIS-APO(a)LRx subcutaneously in an ascending-dose design or placebo (in an 8:2 ratio) at day 1, 3, 5, 8, 15, and 22 (multiple-ascending-dose phase). Primary endpoints were mean percentage change in

  8. Doses of Quercetin in the Range of Serum Concentrations Exert Delipidating Effects in 3T3-L1 Preadipocytes by Acting on Different Stages of Adipogenesis, but Not in Mature Adipocytes

    PubMed Central

    Eseberri, Itziar; Miranda, Jonatan; Lasa, Arrate; Churruca, Itziar; Portillo, María P.

    2015-01-01

    Scope. To determine whether doses of quercetin in the range of serum concentrations exert any effect on triacylglycerol accumulation in maturing preadipocytes and mature adipocytes. The influence on the expression of adipogenic markers as well as on gene expression and activity of enzymes involved in triacylglycerol metabolism were assessed. Methods and Results. 3T3-L1 preadipocytes were treated during differentiation and mature adipocytes for 24 hours with low doses (0.1–10 µM) of quercetin. Triacylglycerol content in both cell types and free fatty acid and glycerol in the incubation medium of mature adipocytes were measured spectrophotometrically. Gene and protein expression were assessed by RT-PCR and Western blot. LPL and FAS activities were quantified. During differentiation quercetin reduced triacylglycerol content at doses from 0.5 to 10 µM. 1 µM of quercetin reduced C/EBPβ gene expression, SREBP1 mature protein levels, and PPARγ gene expression. 10 µM of quercetin reduced LPL gene expression and PPARγ and SREBP1c expression. In mature adipocytes, only 10 µM of quercetin reduced triacylglycerol content. Lipogenic FAS expression and activity were reduced at this dose. Conclusion. Quercetin, in the range of serum concentrations, is able to inhibit adipogenesis, but higher doses, at least 10 µM, are needed to reduce fat accumulation in mature adipocytes. PMID:26180590

  9. Dosimetry of {sup 60}Co and {sup 192}Ir gamma-irradiated agarose gels by proton relaxation time measurement and NMR imaging, in a 0-100 Gy dose range

    SciTech Connect

    Chalansonnet, A.; Briguet, A.; Bonnat, J.L.

    1997-05-01

    Localized irradiation of the skin and subcutaneous tissues with large single doses of gamma rays can induce immediate effects characterized by erythema, desquamation, and necrosis. Correlations between the evolution of the lesions and dosimetry studies have to be established by biophysical methods. NMR studies of the effects of an irradiated Fricke solution might be a means of controlling the delivered irradiation doses. After exposition to ionizing radiations, ferrous ions are transformed into ferric ions. Both are paramagnetic ions, and proton spin-lattice relaxation is accelerated depending on the oxidation reaction. In this study, solution of ammonium ferrous sulfate in an acid environment was incorporated into a gelling substance made with agarose, so that T{sub 1} weighted image contrast could be used to detect ferric ion formation. Experiments with {sup 192}Ir and {sup 90}Co gamma rays with doses in the 0 to 100 Gy range were conducted with Fe{sup 2+} concentrations of 0.5, 1, 1.5, and 2 mM in a gelling substance containing 4% agarose. A relationship was established between the amount of Fe{sup 3+} created and the spin-lattice proton relaxation rate, which led to a straightforward dose-effect relation. The use of such high doses allowed us to reproduce realistic conditions of accidental overexposure. A linear relationship was obtained between the doses absorbed and the NMR parameters measured (T{sub 1} and relative image intensity). 17 refs., 3 figs., 1 tab.

  10. Impact of switching to the ICRP-74 neutron flux-to-dose equivalent rate conversion factors at the Sandia National Laboratory Building 818 Neutron Source Range.

    SciTech Connect

    Ward, Dann C.

    2009-03-01

    Sandia National Laboratories (SNL) maintains a neutron calibration facility which supports the calibration, maintenance, and repair of Radiation Protection Instruments. The SNL neutron reference fields are calibrated using the following methodology: Fluence rate is initially established by calculation using the NIST traceable source emission rate (decay corrected). Correction factors for the effects of room return or scatter, and source anisotropy are then developed by using a suitable radiation transport code to model the geometry of the facility. The conventionally true neutron dose rates are then determined using the appropriate fluence-todose equivalent conversion coefficients at several reference positions. This report describes the impact on calculated neutron dose rates of switching from NCRP-38 to CRP-74 neutron flux-todose equivalent rate conversion factors. This switch is driven by recent changes to dosimetry requirements addressed in 10 CFR 835 (Occupational Radiation Protection).

  11. Barnidipine, a novel calcium antagonist for once-daily treatment of hypertension: a multicenter, double-blind, placebo-controlled, dose-ranging study. Dutch Barnidipine Multicenter Study Group.

    PubMed

    Hart, W; Holwerda, N J

    1997-11-01

    The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95-114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placebo run-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP > or =90 mmHg and a decrease of < 10 mmHg) were treated for an additional 6 weeks with a dose increase of 10 mg. At each clinic visit, sitting and standing blood pressure and heart rate were measured approximately 24 hours after the last dose of study drug was taken. Compared with placebo, barnidipine lowered blood pressure, with a trend toward a dose-response relationship over the dose range 10-30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10-30 mg) administered once daily is well tolerated and reduces blood pressure in patients with mild to moderate hypertension.

  12. Placebo-controlled dose-ranging phase 2 study of subcutaneously administered LHRH antagonist cetrorelix in patients with symptomatic benign prostatic hyperplasia.

    PubMed

    Debruyne, Frans; Gres, Arkadij A; Arustamov, Dmitrii L

    2008-07-01

    Pilot studies with daily dosing suggested the use of the luteinizing hormone-releasing hormone antagonist cetrorelix (CET) for the treatment of symptoms from benign prostatic hyperplasia (BPH). To assess efficacy and safety of three dosing schemes of CET in patients with symptomatic BPH. After a run-in period with 4 weekly injections of placebo, 140 patients with an international prostate symptoms score (IPSS) > or =13 and a peak urinary flow rate (PFR) 5-13ml/s were randomly allocated to 4 treatment groups; patients with residual urine volume of >350ml were excluded. Patients received either CET at dosages of 5mg/wkx4, 10mg/2 wkx2 or 10mg/wkx4 or placebo. IPSS, PFR and mean uroflow, residual urinary volume, prostate volume, plasma testosterone, quality of life, and sexual function were evaluated over a total of 20 wk after randomization. Of 140 randomized patients, one patient did not complete treatment, 5 others dropped out off-treatment, before week 12 evaluation of the primary end point. In all CET groups a rapid improvement in mean IPSS was obtained, with a peak effect of -5.4 to -5.9 (placebo: -2.8). After all dosages of CET given, changes from baseline and differences to placebo were statistically significant up to week 20. Similarly, secondary parameters showed a significant, rapid, and persistent improvement for all CET dosages. All dosage regimens were well tolerated. The study evaluated a single treatment course only; further studies with repeated treatment courses will be required to establish a dose regimen for long-term disease management. At all dosage regimens tested, CET was safe and effective in patients with symptomatic BPH, with a trend towards a more rapid onset of effect for the CET 10mg/wkx4 regimen. Response persisted up to the end of follow-up, 16 wk after the last dose.

  13. The ampakine, Org 26576, bolsters early spatial reference learning and retrieval in the Morris water maze: a subchronic, dose-ranging study in rats.

    PubMed

    Hamlyn, Eugene; Brand, Linda; Shahid, Mohammed; Harvey, Brian H

    2009-10-01

    Ampakines have shown beneficial effects on cognition in selected animal models of learning. However, their ability to modify long-term spatial memory tasks has not been studied yet. This would lend credence to their possible value in treating disorders of cognition. We evaluated the actions of subchronic Org 26576 administration on spatial reference memory performance in the 5-day Morris water maze task in male Sprague-Dawley rats, at doses of 1, 3 and 10 mg/kg twice daily through intraperitoneal injection over 12 days. Org 26576 exerted a dose and time-dependent effect on spatial learning, with dosages of 3 and 10 mg/kg significantly enhancing acquisition on day 1. Globally, escape latency decreased significantly as the training days progressed in the saline and Org 26576-treated groups, indicating that significant and equal learning had taken place over the learning period. However, at the end of the learning period, all doses of Org 26576 significantly improved spatial memory storage/retrieval without confounding effects in the cued version of the task. Org 26576 offers early phase spatial memory benefits in rats, but particularly enhances search accuracy during reference memory retrieval. These results support its possible utility in treating disorders characterized by deficits in cognitive performance.

  14. A single-blind, placebo-controlled, dose-ranging trial of oral hepatic-directed vesicle insulin add-on to oral antidiabetic treatment in patients with type 2 diabetes mellitus.

    PubMed

    Geho, W Blair; Rosenberg, Len N; Schwartz, Sherwyn L; Lau, John R; Gana, Theophilus J

    2014-05-01

    The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3-test-meal/day model in type 2 diabetes patients. The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA(1c) 8.6 ± 2.0% (70.0 ± 21.9 mmol/mol) and on stable metformin therapy. Patients received oral HDV-I capsules daily 30 minutes before breakfast, lunch, and dinner as follows: placebo capsules, 0.05, 0.1, 0.2, and 0.4 U/kg on days 1, 2, 3, 4, and 5, respectively. Outcome measures were PPG and incremental PPG area under the concentration-time curve (AUC). All 4 doses of oral HDV-I statistically significantly lowered mean PPG (P ≤ .0110 each) and incremental PPG (P ≤ .0352 each) AUC compared to placebo. A linear dose response was not observed. The 0.05 U/kg dose was the minimum effective dose in the dosage range studied. Three adverse events unrelated to treatment were observed. Add-on oral HDV-I 0.05-0.4 U/kg significantly lowered PPG excursions and the dose response curve was flat. These results are consistent with the lack of a linear dose response between portal and systemic plasma insulin concentrations in previous animal and human studies. Oral HDV-I was safe and well tolerated.

  15. Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

    PubMed

    Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

    Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

  16. Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study.

    PubMed

    Rhein, Joshua; Morawski, Bozena M; Hullsiek, Kathy Huppler; Nabeta, Henry W; Kiggundu, Reuben; Tugume, Lillian; Musubire, Abdu; Akampurira, Andrew; Smith, Kyle D; Alhadab, Ali; Williams, Darlisha A; Abassi, Mahsa; Bahr, Nathan C; Velamakanni, Sruti S; Fisher, James; Nielsen, Kirsten; Meya, David B; Boulware, David R

    2016-07-01

    Cryptococcus is the most common cause of adult meningitis in Africa. We assessed the safety and microbiological efficacy of adjunctive sertraline, previously shown to have in-vitro and in-vivo activity against cryptococcus. In this open-label dose-finding study, we recruited HIV-infected individuals with cryptococcal meningitis who presented to Mulago Hospital in Kampala, Uganda between Aug 14, 2013, and Aug 30, 2014. To assess safety and tolerability, the first 60 participants were given sertraline at escalating doses of 100 mg/day, 200 mg/day, 300 mg/day, or 400 mg/day as induction therapy for 2 weeks, followed by consolidation therapy with 200 mg/day for an additional 8 weeks. From Nov 29, 2013, participants were randomly assigned (1:1) to receive open-label sertraline at predetermined doses of 200 mg/day, 300 mg/day, or 400 mg/day as induction therapy for 2 weeks, followed by consolidation therapy with 200 mg/day for 8 weeks. Dose assignment was made via computer-generated, permuted block randomisation stratified by antiretroviral therapy (ART) status for people with a first episode of meningitis. The primary outcome was 2-week cerebrospinal fluid (CSF) clearance rate of cryptococcus, termed early fungicidal activity, measured in patients with a first episode of culture-positive meningitis and two or more CSF cultures. This study is registered with ClinicalTrials.gov, number NCT01802385. Of the 330 individuals assessed, 172 HIV-infected adults with cryptococcal meningitis were enrolled. We gave 100 mg/day sertraline to 17 patients, 200 mg/day to 12 patients, 300 mg/day to 14 patients, and 400 mg/day to 17 patients. 112 participants were randomly assigned to receive sertraline at 200 mg (n=48), 300 mg (n=36), or 400 mg (n=28) daily for the first 2 weeks, and 200 mg/day thereafter. The final population consisted of 17 participants in the 100 mg group, 60 in the 200 mg group, 50 in the 300 mg group, and 45 in the 400 mg in group. Participants receiving any

  17. Double-blind trial to find dose range using a fixed combination of mefloquine, sulfadoxine and pyrimethamine in falciparum malaria: a field study on adults in Burma.

    PubMed

    Tin, F; Nyunt Hlaing; Lim, M A; Win, S; Lasserre, R

    1987-01-01

    In a field study conducted in Burma, 60 semi-immune adults were randomly assigned to 2 treatment groups. The first (mean parasite count, 12717/mm3) received a single dose of a fixed combination of 500 mg mefloquine base, 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets of 'Fansimef') plus 1 tablet placebo. The second group (mean parasite count, 11 863/mm3) were given 3 tablets of the same medication. The study was double-blind. Parasite count was checked daily for the first week and weekly for a further 3 weeks. Average times for parasite clearance were 1.47 d in patients receiving 2 tablets, and 1.87 d in those given 3 tablets. Asexual parasites reappeared on day 28 in one patient in each group, although they had been free of parasites during the previous 4 weeks; this could be due to reinfection. The drugs were generally well tolerated, though mild and transient giddiness was seen in 80% of patients in the first group and 96% in the second. Nausea was reported by 33% and 43% of patients respectively. No vomiting occurred in the first group but 8 patients vomited in the second (P less than 0.01). In conclusion it seems possible to treat falciparum malaria in semi-immune adults, weighing less than 60 kg, with a single dose of 500 mg mefloquine base, 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets), instead of the higher dose (3 tablets) currently recommended. This reduces treatment cost and improves tolerance of the drugs.

  18. Digestive tolerance of inulin-type fructans: a double-blind, placebo-controlled, cross-over, dose-ranging, randomized study in healthy volunteers.

    PubMed

    Bruhwyler, Jacques; Carreer, Fabienne; Demanet, Etienne; Jacobs, Heidi

    2009-03-01

    Similar to other indigestible carbohydrates or dietary fibres, a consumption of too large quantities of inulin-type fructans may cause some digestive problems. To compare the digestive tolerance of inulin-type fructans, administered during 2 weeks, at different doses. Eighty-four healthy volunteers (aged 18-45 years, mean body mass index 25.1 kg/m2 and mean total fibre consumption 12 g) were included in a double-blind, placebo-controlled, randomized, cross-over study comparing Fibrulose F97 (5 and 20 g/day), Fibruline Instant (5, 10 and 20 g/day) and Fibruline XL (10 g/day) (degrees of polymerization respectively equal to 2-20, 2-60 with an average of 10, and 2-60 with an average >20) to placebo. The study was decomposed into five 2-week periods: placebo run-in, treatment 1, placebo washout, treatment 2, placebo run-out. The following symptoms were assessed using visual analogue scales: flatulence, rumbling, bloating, abdominal pain, abdominal cramps, nausea, stool frequency and stool consistency. The primary variable was the mean difference between treatment and placebo in terms of tolerance (sum of the eight visual analogue scales). The three products tended to increase digestive symptoms whatever the dose but the change was mild (maximum, +19 mm on the 800-mm scale) and significant (P<0.001) for Fibruline Instant at 20 g/day only. At 20 g/day, a statistically significant difference between Fibruline Instant and Fibrulose F97 was demonstrated (P=0.011). There was a dose-effect relationship both for Fibrulose F97 (P>0.05) and Fibruline Instant (P=0.042). All the other tendencies were non-significant. The three different inulin-type fructans were very well tolerated.

  19. Passive dosing of triclosan in multigeneration tests with copepods - stable exposure concentrations and effects at the low μg/L range.

    PubMed

    Ribbenstedt, Anton; Mustajärvi, Lukas; Breitholtz, Magnus; Gorokhova, Elena; Mayer, Philipp; Sobek, Anna

    2017-05-01

    Ecotoxicity testing is a crucial component of chemical risk assessment. Still, due to methodological difficulties related to controlling exposure concentrations over time, data on long-term effects of organic chemicals at low concentrations are limited. The aim of the present study was, therefore, to test the applicability of passive dosing to maintain stable concentrations of the organochlorine bacteriocide triclosan in the water phase during a 6-wk multigeneration population development test with the harpacticoid copepod Nitocra spinipes. Triclosan was loaded into silicone (1000 mg), which was used as passive dosing phase in the exposure vials. The distribution ratio for triclosan between silicone and water (Dsilicone-water ) was 10466 ± 1927. A population development test was conducted at 3 concentration levels of triclosan that were measured to be 3 μg/L to 5 μg/L, 7 μg/L to 11 μg/L and 16 μg/L to 26 μg/L. The results demonstrate that passive dosing is applicable for long-term ecotoxicity testing of organic chemicals, including during significant growth of the test organism population. Shifts in the demographic structure of the population during exposure suggest the most severe effects were exerted on juvenile development. Progressively lower development index values in the populations exposed to increasing triclosan concentrations suggest developmental retardation. The results further stress the need for chronic exposure during ecotoxicity testing in chemical risk assessment because even the most sensitive endpoint was not significant until after 7 d of exposure. Environ Toxicol Chem 2017;36:1254-1260. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

  20. Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.

    PubMed

    Jatlow, Peter I; Agro, Ann; Wu, Ran; Nadim, Haleh; Toll, Benjamin A; Ralevski, Elizabeth; Nogueira, Christine; Shi, Julia; Dziura, James D; Petrakis, Ismene L; O'Malley, Stephanie S

    2014-07-01

    The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results with self-reports in clinical trials. Subjects (n = 18) were administered, 1 week apart, 3 alcohol doses calibrated to achieve blood concentrations of 20, 80, and 120 mg/dl, respectively. Urinary EtG/EtS was measured at timed intervals during a 24-hour hospitalization and twice daily thereafter. In addition, participants from 2 clinical trials provided samples for EtG/EtS and drinking histories. Cutoffs for EtG/EtS of 100/50, 200/100, and 500/250 ng/ml were evaluated. Twelve hours following each challenge, EtG was always positive at the 100 and 200 cutoffs, but at 24 hours sensitivity was poor at all cutoffs following the low dose, and poor after 48 hours regardless of dose or cutoff. Similarly, in the clinical trials EtG sensitivity was good for detecting any drinking during the last 24 hours at the 2 lowest cutoffs, but under 40% during the last 24 to 48 hours. Sensitivity was reduced at the 500 ng/ml cutoff. Discrepancies between EtG and EtS were few. Comparison of self-reports of abstinence and EtG-confirmed abstinence indicated underreporting of drinking. Any drinking the night before should be detectable the following morning with EtG cutoffs of 100 or 200 ng/ml. Twenty-four hours after drinking, sensitivity is poor for light drinking, but good for heavier consumption. At 48 hours, sensitivity is low following 6 drinks or less. Increasing the cutoff to 500 ng/ml leads to substantially reduced sensitivity. Monitoring both EtG and EtS should usually be unnecessary. We recommend EtG-confirmed self-reports of abstinence for evaluation of outcomes in clinical trials. Copyright © 2014 by the Research Society on Alcoholism.

  1. Ethylglucuronide and Ethyl Sulfate Assays in Clinical Trials, Interpretation and Limitations: Results of a Dose Ranging Alcohol Challenge Study and Two Clinical Trials

    PubMed Central

    Jatlow, Peter I.; Agro, Ann; Wu, Ran; Nadim, Haleh; Toll, Benjamin A.; Ralevski, Elizabeth; Nogueira, Christine; Shi, Julia; Dziura, James D.; Petrakis, Ismene L.; O'Malley, Stephanie S.

    2014-01-01

    Background The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS) are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results with self-reports in clinical trials. Methods Subjects (n=18) were administered, one week apart, 3 alcohol doses calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL respectively. Urinary EtG/EtS were measured at timed intervals during a 24 hour hospitalization and twice daily thereafter. In addition, participants from 2 clinical trials provided samples for EtG/EtS and drinking histories. Cutoffs for EtG/EtS of 100/50, 200/100 and 500/250 ng/mL were evaluated. Results Twelve hours following each challenge, EtG was always positive at the 100 and 200 cutoffs, but at 24 hours sensitivity was poor at all cutoffs following the low dose, and poor after 48 hours regardless of dose or cutoff. Similarly, in the clinical trials EtG sensitivity was good for detecting any drinking during the last 24 hours at the two lowest cutoffs, but under 40% during the last 24-48 hours. Sensitivity was reduced at the 500 ng/mL cutoff. Discrepancies between EtG and EtS were few. Comparison of self- reports of abstinence and EtG confirmed abstinence indicated under-reporting of drinking. Conclusions Any drinking the night before should be detectable the following morning with EtG cutoffs of 100 or 200 ng/mL. Twenty-four hours after drinking, sensitivity is poor for light drinking, but good for heavier consumption. At 48 hours, sensitivity is low following 6 drinks or less. Increasing the cutoff to 500 ng/mL leads to substantially reduced sensitivity. Monitoring both EtG and EtS should usually be unnecessary. We recommend EtG confirmed self-reports of abstinence for evaluation of outcomes in clinical trials. PMID:24773137

  2. Egg hatching response to a range of ultraviolet-B (UV-B) radiation doses for four predatory mites and the herbivorous spider mite Tetranychus urticae.

    PubMed

    Koveos, Dimitrios S; Suzuki, Takeshi; Terzidou, Anastasia; Kokkari, Anastasia; Floros, George; Damos, Petros; Kouloussis, Nikos A

    2017-01-01

    Egg hatchability of four predatory mites-Phytoseiulus persimilis Athias-Henriot, Iphiseius [Amblyseius] degenerans Berlese, Amblyseius swirskii Athias-Henriot, and Euseius finlandicus Oudemans (Acari: Phytoseiidae)-and the spider mite Tetranychus urticae Koch (Acari: Tetranychidae) was determined under various UV-B doses either in constant darkness (DD) or with simultaneous irradiation using white light. Under UV-B irradiation and DD or simultaneous irradiation with white light, the predator's eggs hatched in significantly lower percentages than in the control non-exposed eggs, which indicates deleterious effects of UV-B on embryonic development. In addition, higher hatchability percentages were observed under UV-B irradiation and DD in eggs of the predatory mites than in eggs of T. urticae. This might be caused by a higher involvement of an antioxidant system, shield effects by pigments or a mere shorter duration of embryonic development in predatory mites than in T. urticae, thus avoiding accumulative effects of UV-B. Although no eggs of T. urticae hatched under UV-B irradiation and DD, variable hatchability percentages were observed under simultaneous irradiation with white light, which suggests the involvement of a photoreactivation system that reduces UV-B damages. Under the same doses with simultaneous irradiation with white light, eggs of T. urticae displayed higher photoreactivation and were more tolerant to UV-B than eggs of the predatory mites. Among predators variation regarding the tolerance to UV-B effects was observed, with eggs of P. persimilis and I. degenerans being more tolerant to UV-B radiation than eggs of A. swirskii and E. finlandicus.

  3. SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

    SciTech Connect

    Sahoo, N; Zhu, X; Zhang, X; Poenisch, F; Li, H; Wu, R; Lii, M; Umfleet, W; Gillin, M; Mahajan, A; Grosshans, D

    2014-06-01

    Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-case dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.

  4. Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study.

    PubMed

    Schlesinger, Naomi; De Meulemeester, Marc; Pikhlak, Andrey; Yücel, A Eftal; Richard, Dominik; Murphy, Valda; Arulmani, Udayasankar; Sallstig, Peter; So, Alexander

    2011-03-25

    We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab

  5. Efficacy of Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis: an open-label dose-ranging study

    PubMed Central

    Rhein, Joshua; Morawski, Bozena M; Hullsiek, Kathy Huppler; Nabeta, Henry W; Kiggundu, Reuben; Tugume, Lillian; Musubire, Abdu; Akampurira, Andrew; Smith, Kyle D; Alhadab, Ali; Williams, Darlisha A; Abassi, Mahsa; Bahr, Nathan C; Velamakanni, Sruti S; Fisher, James; Nielsen, Kirsten; Meya, David B; Boulware, David R

    2016-01-01

    Background Cryptococcus is the most common cause of adult meningitis in Africa. We evaluated the activity of adjunctive sertraline, previously demonstrated to have in vitro and in vivo activity against Cryptococcus. Methods We enrolled 172 HIV-infected Ugandans with cryptococcal meningitis from August 2013 through August 2014 into an open-label dose-finding study to assess safety and microbiologic efficacy. Sertraline 100–400mg/day was added to standard therapy of amphotericin + fluconazole 800mg/day. We evaluated early fungicidal activity via Cryptococcus cerebrospinal fluid (CSF) clearance rate, sertraline pharmacokinetics, and in vitro susceptibility. Findings Participants receiving any sertraline dose averaged a CSF clearance rate of −0·37 (95%CI: −0·41, −0·33) colony forming units (CFU)/mL/day. Incidence of paradoxical immune reconstitution inflammatory syndrome (IRIS) was 5% (2/43) and relapse was 0% through 12-weeks. Sertraline reached steady state concentrations in plasma by day 7, with median steady-state concentrations of 201 ng/mL (IQR, 90–300; n=49) with 200mg/day and 399 ng/mL (IQR, 279–560; n=30) with 400mg/day. Plasma concentrations reached 83% of steady state levels by day 3. The median projected steady state brain tissue concentration at 200mg/day was 3·7 (IQR, 2·0–5·7) mcg/mL and 6·8 (IQR, 4·6–9·7) mcg/mL at 400mg/day. Minimum inhibitory concentrations were ≤2 mcg/mL for 27% (35/128), ≤4 mcg/mL for 84% (108/128), ≤6 mcg/mL for 91% (117/128), and ≤8 mcg/mL for 100% of 128 Cryptococcus isolates. Interpretation Sertraline had faster cryptococcal CSF clearance, decreased IRIS, and decreased relapse compared with historical experiences. Sertraline reaches therapeutic levels in a clinical setting. This inexpensive and off-patent oral medication is a promising adjunctive antifungal therapy. Funding National Institutes of Health, Grand Challenges Canada. PMID:26971081

  6. Reactogenicity and immunogenicity profiles of a novel pentavalent diphtheria-tetanus-whole cell pertussis-hepatitis B and Haemophilus influenzae type B vaccine: a randomized dose-ranging trial of the Hib tetanus-conjugate content.

    PubMed

    Hla, Khin Hla; Thein, Saw Aung Myat; Aye, Aye; Han, Htay-Htay; Bock, Hans L; David, Marie-Pierre; Schuerman, Lode

    2006-08-01

    Combined vaccines containing diphtheria-tetanus-pertussis whole-cell (DTPw), Haemophilus influenzae type b (Hib), and hepatitis-B vaccines are essential for the continuing success of vaccination programs in developing nations. This randomized, dose-ranging study assessed the immunogenicity and reactogenicity of primary and booster vaccination with pentavalent DTPw-HBV/Hib vaccines containing 10, 5 or 2.5 microg of polyribosylribitol phosphate (PRP) conjugated to tetanus toxoid (trials Hib-052/064). Six hundred eighty infants were randomized to receive one of 5 vaccine combinations at 6, 10, and 14 weeks of age. Of these, 351 received the same vaccine at 15-24 months of age. The immune response was evaluated on blood samples collected 1 month after the 3-dose primary course and before and 6 weeks after the booster dose. Reactogenicity was assessed during a 4-day period after each vaccine dose using diary cards. After primary vaccination, all subjects had seroprotective anti-PRP antibody concentrations (> or = 0.15 microg/mL) and > 95% had concentrations > or = 1.0 microg/mL, irrespective of the PRP dose administered. Anti-PRP antibody avidity after primary vaccination and antibody persistence until the second year of life were similar among groups. The booster dose induced marked increases in anti-PRP antibody GMCs and antibody avidity, indicative of effective priming and the presence of immune memory. All vaccination regimens elicited good immune responses and comparable antibody persistence to the other vaccine antigens, with significant increases in all antibody concentrations observed after boosting. All vaccination regimens were safe, with similar overall reactogenicity profiles. Hib conjugate vaccines containing reduced amounts of PRP can be effectively combined with the licensed DTPw-HBV vaccine to provide protection against 5 major childhood pathogens in a single injection.

  7. Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study.

    PubMed

    Chopra, Arvind; Chandrashekara, S; Iyer, Rajgopalan; Rajasekhar, Liza; Shetty, Naresh; Veeravalli, Sarathchandra Mouli; Ghosh, Alakendu; Merchant, Mrugank; Oak, Jyotsna; Londhey, Vikram; Barve, Abhijit; Ramakrishnan, M S; Montero, Enrique

    2016-04-01

    The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).

  8. Results of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia.

    PubMed

    Ballantyne, Christie M; Neutel, Joel; Cropp, Anne; Duggan, William; Wang, Ellen Q; Plowchalk, David; Sweeney, Kevin; Kaila, Nitin; Vincent, John; Bays, Harold

    2015-05-01

    Bococizumab is a humanized monoclonal antibody binding proprotein convertase subtilisin/kexin type 9, which may be a potential therapeutic option for reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. In this 24-week, multicenter, double-blind, placebo-controlled, dose-ranging study (NCT01592240), subjects with LDL-C levels≥80 mg/dl on stable statin therapy were randomized to Q14 days subcutaneous placebo or bococizumab 50, 100, or 150 mg or Q28 days subcutaneous placebo or bococizumab 200 or 300 mg. Doses of bococizumab were reduced if LDL-C levels persistently decreased to ≤25 mg/dl. The primary end point was the absolute change in LDL-C levels from baseline to week 12 after placebo or bococizumab administration. Continuation of bococizumab administration through to week 24 enabled the collection of safety data over an extended period. Of the 354 subjects randomized, 351 received treatment (placebo [n=100] or bococizumab [n=251]). The most efficacious bococizumab doses were 150 mg Q14 days and 300 mg Q28 days. Compared with placebo, bococizumab 150 mg Q14 days reduced LDL-C at week 12 by 53.4 mg/dl and bococizumab 300 mg Q28 days reduced LDL-C by 44.9 mg/dl; this was despite dose reductions in 32.5% and 34.2% of subjects at week 10 or 8, respectively. Pharmacokinetic/pharmacodynamic model-based simulation assuming no dose reductions predicted that bococizumab would lower LDL-C levels by 72.2 and 55.4 mg/dl, respectively. Adverse events were similar across placebo and bococizumab groups. Few subjects (n=7; 2%) discontinued treatment because of treatment-related adverse events. In conclusion, bococizumab significantly reduced LDL-C across all doses despite dose reductions in many subjects. Model-based simulations predicted greater LDL-C reduction in the absence of bococizumab dose reduction. The Q14 days regimen is being evaluated in phase 3 clinical trials.

  9. A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Belimumab in Patients With Active Systemic Lupus Erythematosus

    PubMed Central

    Wallace, Daniel J.; Stohl, William; Furie, Richard A.; Lisse, Jeffrey R.; McKay, James D.; Merrill, Joan T.; Petri, Michelle A.; Ginzler, Ellen M.; Chatham, W. Winn; McCune, W. Joseph; Fernandez, Vivian; Chevrier, Marc R.; Zhong, John; Freimuth, William W.

    2009-01-01

    Objective To assess the safety, tolerability, biological activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Methods Patients with SELENA-SLEDAI score≥4 (N=449) were randomly assigned to belimumab (1, 4, 10 mg/kg) or placebo in a 52-week study. Co-primary endpoints were: 1) percentage change in the SELENA-SLEDAI score at week 24; 2) time to the first SLE flare. Results Significant differences between the treatment and placebo groups were not attained for either primary endpoint and no dose response was observed. Reduction in SELENA-SLEDAI score from baseline was 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24–52 was significantly longer with belimumab treatment (154 versus 108 days; P=0.0361). In the subgroup (71.5%) of serologically active patients (ANA ≥1:80 and/or anti-dsDNA ≥30 IU/mL), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI (−28.8% versus −14.2%; P=0.0435); PGA (−32.7% versus −10.7%; P=0.0011); and SF-36 PCS (+3.0 versus +1.2 points; P=0.0410). Treatment with belimumab resulted in 63–71% depletion of naive, activated, and plasmacytoid CD20+ B cells and a 29.4% reduction in anti-dsDNA titers (P ≤0.0017) by week 52. The rates of adverse events (AEs) and serious AEs were similar in the belimumab and placebo groups. Conclusion Belimumab was biologically active and well tolerated. Belimumab effect on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than SOC alone. PMID:19714604

  10. Efficacy, Safety, and Tolerability of Fulranumab as an Adjunctive Therapy in Patients With Inadequately Controlled, Moderate-to-Severe Chronic Low Back Pain: A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Dose-loading Phase II Study.

    PubMed

    Sanga, Panna; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Thipphawong, John

    2016-06-01

    Fulranumab is an investigational, fully human recombinant monoclonal antibody (IgG2) that neutralizes the biological actions of human nerve growth factor. Low back pain is a common cause of noncancer chronic pain and represents one of the most significant socioeconomic health-related problems in developed countries. This randomized, double-blind, placebo-controlled study was conducted to evaluate the analgesic effect of fulranumab in patients with moderate-to-severe chronic low back pain. Patients (aged 18-80 years) were randomized to receive subcutaneous injections every 4 weeks in 1 of 5 parallel treatment groups: placebo or fulranumab 1mg (1mgQ4wk), 3mg (3mgQ4wk), 3mg after a 6mg loading dose (6mgLD+3mgQ4wk), or 10mg (10mgQ4wk) every 4 weeks. A total of 385 patients (median age, 53 years; women, 54%) received at least 1 injection of study medication. No statistically significant differences were observed in improvement of pain intensity scores between the fulranumab treatment regimens and the placebo group at week 12 (primary end point; mean [SD], placebo: -2.0 [2.17], 1mgQ4wk: -1.9 [2.14], 3mgQ4wk: -2.2 [1.89], 6mgLD+3mgQ4wk: -2.0 [1.72] and 10mgQ4wk: -2.1 [2.18]). Results for secondary efficacy parameters (change in the Oswestry Disability Index, Brief Pain Inventory-Short Form, and Patient Global Assessment scales) were consistent with the primary outcome. A placebo effect was observed; the overall percentage of patients with treatment-emergent adverse events (TEAEs) was similar between the placebo (76%) and fulranumab treatment groups (77%-90%). Across all phases, the most common TEAEs in at least 10% of patients (combined fulranumab group vs placebo) were arthralgia (15% vs 12%), back pain (15% vs 18%), upper respiratory tract infection (15% vs 8%), paresthesia (14% vs 8%), diarrhea (12% vs 4%), headache (12% vs 8%), hypoesthesia (11% vs 5%), pain in extremity (11% vs 8%), sinusitis (10% vs 5%), and nasopharyngitis (10% vs 9%). Across all phases, neurologic

  11. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial.

    PubMed

    van Lunzen, Jan; Maggiolo, Franco; Arribas, José R; Rakhmanova, Aza; Yeni, Patrick; Young, Benjamin; Rockstroh, Jürgen K; Almond, Steve; Song, Ivy; Brothers, Cindy; Min, Sherene

    2012-02-01

    Dolutegravir (S/GSK1349572) is a new HIV-1 integrase inhibitor that has antiviral activity with once daily, unboosted dosing. SPRING-1 is an ongoing study designed to select a dose for phase 3 assessment. We present data from preplanned primary and interim analyses. In a phase 2b, multicentre, dose-ranging study, treatment-naive adults were randomly assigned (1:1:1:1) to receive 10 mg, 25 mg, or 50 mg dolutegravir or 600 mg efavirenz. Dose but not drug allocation was masked. Randomisation was by a central integrated voice-response system according to a computer-generated code. Study drugs were given with either tenofovir plus emtricitabine or abacavir plus lamivudine. Our study was done at 34 sites in France, Germany, Italy, Russia, Spain, and the USA beginning on July 9, 2009. Eligible participants were seropositive for HIV-1, aged 18 years or older, and had plasma HIV RNA viral loads of at least 1000 copies per mL and CD4 counts of at least 200 cells per μL. Our primary endpoint was the proportion of participants with viral load of less than 50 copies per mL at week 16 and we present data to week 48. Analyses were done on the basis of allocation group and included all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00951015. 205 patients were randomly allocated and received at least one dose of study drug: 53, 51, and 51 to receive 10 mg, 25 mg, and 50 mg dolutegravir, respectively, and 50 to receive efavirenz. Week 16 response rates to viral loads of at most 50 copies per mL were 93% (144 of 155 participants) for all doses of dolutegravir (with little difference between dose groups) and 60% (30 of 50) for efavirenz; week 48 response rates were 87% (139 of 155) for all doses of dolutegravir and 82% (41 of 50) for efavirenz. Response rates between nucleoside reverse transcriptase inhibitor subgroups were similar. We identified three virological failures in the dolutegravir groups and one in

  12. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study

    PubMed Central

    Giugliano, Robert P; Desai, Nihar R; Kohli, Payal; Rogers, William J; Somaratne, Ransi; Huang, Fannie; Liu, Thomas; Mohanavelu, Satishkumar; Hoffman, Elaine B; McDonald, Shannon T; Abrahamsen, Timothy E; Wasserman, Scott M; Scott, Robert; Sabatine, Marc S

    2013-01-01

    Summary Background LDL cholesterol (LDL-C) is a well established risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation. We therefore assessed the efficacy, safety, and tolerability of AMG 145, a human monoclonal IgG2 antibody against PCSK9, in stable patients with hypercholesterolemia on a statin. Methods In a phase 2, dose-ranging study done in 78 centres in the USA, Canada, Denmark, Hungary, and Czech Republic, patients (aged 18–80 years) with LDL-C greater than 2.2 mmol/L on a stable dose of statin (with or without ezetimibe), were randomly assigned equally, through an interactive voice response system, to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or matching placebo every 2 weeks; or subcutaneous injections of AMG 145 280 mg, 350 mg, or 420 mg, or matching placebo every 4 weeks. Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules. The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01380730. Findings 631 patients with hypercholesterolaemia were randomly assigned to AMG 145 70 mg (n=79), 105 mg (n=79), or 140 mg (n=78), or matching placebo (n=78) every 2 weeks; or AMG 145 280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79) every 4 weeks. At the end of the dosing interval at week 12, the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks (ranging from 41.8% to 66.1%; p<0.0001 for each dose vs placebo) and AMG 145 every 4 weeks (ranging from 41.8% to 50.3%; p<0.0001). No treatment-related serious adverse events occurred. The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups (39 [8%] of 474 vs 11 [7%] of 155); none of these events were severe or life

  13. Hormesis and Paradoxical Effects of Wheat Seedling (Triticum Aestivum L.) Parameters Upon Exposure to Different Pollutants in a Wide Range of Doses

    PubMed Central

    Erofeeva, Elena A.

    2014-01-01

    Chlorophyll and carotenoid content (ChCar), lipid peroxidation (LP) and growth parameters (GP) in plants are often used for environmental pollution estimation. However, the nonmonotonic dose–response dependences (hormesis and paradoxical effects) of these indices are insufficiently explored following exposure to different pollutants. In this experiment, we studied nonmonotonic changes in ChCar, LP, GP in wheat seedlings (Triticum aestivum L.) upon exposure to lead, cadmium, copper, manganese, formaldehyde, the herbicide glyphosate, and sodium chloride in a wide range from sublethal concentration to 102–105 times lower concentrations. 85.7% of dose–response dependences were nonmonotonic (of these, 5.5% were hormesis and paradoxical effects comprised 94.5%). Multiphasic dependences were the most widespread type of paradoxical effect. Hormesis was a part of some multiphasic responses (i.e. paradoxical effects), which indicates a relationship between these phenomena. Sublethal pollutant concentrations significantly increased LP (to 2.0–2.4 times, except for manganese and glyphosate) and decreased GP (to 2.1–36.6 times, except for glyphosate), while ChCar was reduced insignificantly, normalized or even increased. Lower pollutant concentrations caused a moderate deviation in all parameters from the control (not more than 62%) for hormesis and paradoxical effects. The seedling parameters could have different types of nonmonotonic responses upon exposure to the same pollutant. PMID:24659937

  14. 40 CFR 3.20 - How will EPA provide notice of changes to the Central Data Exchange?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false How will EPA provide notice of changes to the Central Data Exchange? 3.20 Section 3.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL CROSS-MEDIA ELECTRONIC REPORTING Electronic Reporting to EPA § 3.20 How will EPA provide...

  15. Deletion of chromosome 3 and a 3;20 reciprocal translocation demonstrated by chromosome painting

    SciTech Connect

    Crispino, B.; Cardoso, H.; Mimbacas, A.

    1995-01-02

    The combined use of high resolution banding and chromosome painting techniques allowed us to identify a reciprocal translocation involving chromosomes 3 and 20 and simultaneous interstitial deletion of chromosome 3 in a patient with several minor anomalies of the face and hands. His karyotype is described as 46,XY,t(3;20) (p14.2;p12.2),del(3)(p11-p14.1). 25 refs., 3 figs.

  16. Geometric, stability, and electronic properties of gold-doped Pd clusters (Pd n Au, n = 3 20)

    NASA Astrophysics Data System (ADS)

    Huan, Hao; Chen, Yan; Wang, Tao; Ye, Xiang; Gu, Xiao

    2016-11-01

    The structure, stability, and electronic properties of Pd n Au ( n = 3 20) clusters are studied by density functional theory. The results show that the clusters studied here prefer three-dimensional structures even with very small atom number. It is found that the binding energies of Pd n Au clusters are higher than the corresponding pure Pd n clusters with the same atom number. Most Pd n Au clusters studied here are magnetic with magnetic moments ranging from 1.0 to 7.0 μ B. The dissociation energies of Pd atoms are lower than the doped gold atom, that is the doped Au atom will increase the mother clusters stability and activity.

  17. Regulation of a putative corticosteroid, 17, 21-dihydroxypregn-4-ene, 3, 20-one, in sea lamprey, Petromyzon marinus.

    USGS Publications Warehouse

    Roberts, Brent W.; Didier, Wes; Satbir, Rai; Johnson, Nicholas S.; Libants, Scot V.; Sang-Seon, Yun; Close, David

    2013-01-01

    In higher vertebrates, in response to stress, the hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates cells in the anterior pituitary to produce adrenocorticotropic hormone (ACTH), which in turn stimulates production of either cortisol (F) or corticosterone (B) by the adrenal tissues. In lampreys, however, neither of these steroids is present. Instead, it has been proposed that the stress steroid is actually 17,21-dihydroxypregn-4-ene-3,20-dione (11-deoxycortisol; S). However, there have been no studies yet to determine its mechanism of regulation or site of production. Here we demonstrate that (1) intraperitoneal injections of lamprey-CRH increase plasma S in a dose dependent manner, (2) intraperitoneal injections of four lamprey-specific ACTH peptides at 100 lg/kg, did not induce changes in plasma S concentrations in either males or females; (3) two lamprey-specific gonadotropin-releasing hormones (GnRH I and III) and arginine-vasotocin (AVT), all at single doses, stimulated S production as well as, or to an even greater extent than CRH; (4) sea lamprey mesonephric kidneys, in vitro, converted tritiated 17a-hydroxyprogesterone (17a-P) into a steroid that had the same chromatographic properties (on HPLC and TLC) as S; (5) kidney tissues released significantly more immunoassayable S into the incubation medium than gill, liver or gonad tissues. One interpretation of these results is that the corticosteroid production of the sea lamprey, one of the oldest extant vertebrates, is regulated through multiple pathways rather than the classical HPI-axis. However, the responsiveness of this steroid to the GnRH peptides means that a reproductive rather than a stress role for this steroid cannot yet be ruled out.

  18. Regulation of a putative corticosteroid, 17,21-dihydroxypregn-4-ene,3,20-one, in sea lamprey, Petromyzon marinus.

    PubMed

    Roberts, Brent W; Didier, Wes; Rai, Satbir; Johnson, Nicholas S; Libants, Scot; Yun, Sang-Seon; Close, David A

    2014-01-15

    In higher vertebrates, in response to stress, the hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates cells in the anterior pituitary to produce adrenocorticotropic hormone (ACTH), which in turn stimulates production of either cortisol (F) or corticosterone (B) by the adrenal tissues. In lampreys, however, neither of these steroids is present. Instead, it has been proposed that the stress steroid is actually 17,21-dihydroxypregn-4-ene-3,20-dione (11-deoxycortisol; S). However, there have been no studies yet to determine its mechanism of regulation or site of production. Here we demonstrate that (1) intraperitoneal injections of lamprey-CRH increase plasma S in a dose dependent manner, (2) intraperitoneal injections of four lamprey-specific ACTH peptides at 100μg/kg, did not induce changes in plasma S concentrations in either males or females; (3) two lamprey-specific gonadotropin-releasing hormones (GnRH I and III) and arginine-vasotocin (AVT), all at single doses, stimulated S production as well as, or to an even greater extent than CRH; (4) sea lamprey mesonephric kidneys, in vitro, converted tritiated 17α-hydroxyprogesterone (17α-P) into a steroid that had the same chromatographic properties (on HPLC and TLC) as S; (5) kidney tissues released significantly more immunoassayable S into the incubation medium than gill, liver or gonad tissues. One interpretation of these results is that the corticosteroid production of the sea lamprey, one of the oldest extant vertebrates, is regulated through multiple pathways rather than the classical HPI-axis. However, the responsiveness of this steroid to the GnRH peptides means that a reproductive rather than a stress role for this steroid cannot yet be ruled out.

  19. A multicenter, randomized, double-blind dose-ranging study of glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler compared to the monocomponents and open-label tiotropium dry powder inhaler in patients with moderate-to-severe COPD.

    PubMed

    Tashkin, Donald P; Martinez, Fernando J; Rodriguez-Roisin, Roberto; Fogarty, Charles; Gotfried, Mark; Denenberg, Michael; Gottschlich, Gregory; Donohue, James F; Orevillo, Chad; Darken, Patrick; St Rose, Earl; Strom, Shannon; Fischer, Tracy; Golden, Michael; Reisner, Colin

    2016-11-01

    This study formed part of the dose selection for a glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination formulated using novel Co-Suspension™ Delivery Technology and delivered via a metered dose inhaler (GFF MDI). The study aimed to confirm the optimal dose of GP to formulate with FF 9.6 μg in the fixed-dose combination product, GFF MDI. This multicenter, randomized, double-blind, chronic-dosing, balanced incomplete block, crossover study (NCT01587079) compared five doses of GFF MDI (18/9.6, 9/9.6, 4.6/9.6, 2.4/9.6 and 1.2/9.6 μg, twice daily [BID]) with its monocomponents FF MDI 9.6 μg and GP MDI 18 μg (both BID) and open-label tiotropium (18 μg once daily) as the active control. The primary efficacy endpoint was change from baseline in forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 7. In total, 159 patients were randomized to treatment and 132 patients (52.2% male, mean age 62.8 years) were included in the intent-to-treat population. All doses of GFF MDI (except 1.2/9.6 μg) resulted in statistically significant improvements in FEV1 AUC0-12 versus monocomponents and open-label tiotropium. GFF MDI 18/9.6 μg consistently showing the greatest improvement over monocomponents and open-label tiotropium. Adverse events for each GFF MDI dose were similar versus GP MDI 18 μg, FF MDI 9.6 μg and open-label tiotropium. These findings further support selection of GP 18 μg as the optimal dose to combine with FF MDI 9.6 μg for advancement into Phase III clinical trials of GFF MDI. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

    PubMed

    Provenzano, Robert; Besarab, Anatole; Wright, Steven; Dua, Sohan; Zeig, Steven; Nguyen, Peter; Poole, Lona; Saikali, Khalil G; Saha, Gopal; Hemmerich, Stefan; Szczech, Lynda; Yu, K H Peony; Neff, Thomas B

    2016-06-01

    Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total

  1. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY).

    PubMed

    Abrams, P; Kelleher, C; Staskin, D; Kay, R; Martan, A; Mincik, I; Newgreen, D; Ridder, A; Paireddy, A; van Maanen, R

    2017-05-01

    This large dose-ranging study explored the benefits of different combinations of mirabegron and solifenacin on health-related quality of life (HRQoL), based on patient-reported outcomes (PROs), and patients ('responders') achieving clinically meaningful improvements in efficacy and HRQoL. SYMPHONY (NCT01340027) was a Phase II, placebo- and monotherapy-controlled, dose-ranging, 12-week trial. Adult patients with overactive bladder (OAB) for ≥3 months were randomized to 1 of 12 groups: 6 combination (solifenacin 2.5/5/10 mg + mirabegron 25/50 mg), 5 monotherapy (solifenacin 2.5/5/10 mg, or mirabegron 25/50 mg), or placebo. Change from baseline to end of treatment was assessed, versus placebo and solifenacin 5 mg in: PROs (OAB-q [Symptom Bother/total HRQoL] and Patient Perception of Bladder Condition score), and responders achieving minimally important differences (MIDs) in PROs and predetermined clinically meaningful improvements in efficacy (e.g. <8 micturitions/24 h). Changes in PROs and responders were analysed using an ANCOVA model and logistic regression, respectively. The Full Analysis Set included 1278 patients. Combination therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs versus solifenacin 5 mg and placebo, and significantly more responders achieved MIDs in PROs and efficacy. Micturition frequency normalization was approximately twofold greater with 10 + 25 mg (OR 2.06 [95 % CI 1.11, 3.84; p = 0.023]) and 5 + 50 mg (OR 1.91 [95 % CI 1.14, 3.21; p = 0.015]) versus solifenacin 5 mg. Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.

  2. Influence of age on flurbiprofen axetil requirements for preventing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study.

    PubMed

    Fujii, Yoshitaka; Nakayama, Masahiro

    2006-08-01

    Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Preceded by venous occlusion, flurbiprofen axetil, a prodrug of the NSAID flurbiprofen, has been associated with a reduction in pain induced by propofol injection. A review of the literature determined that no published data were available on the influence of age on the requirements for flurbiprofen axetil dose. This study was undertaken to examine the influence of age on flurbiprofen axetil requirements for the treatment of propofol-induced pain on injection in Japanese adult surgical patients. This prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study was conducted at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Young (age 20-40 years) and older (age 60-80 years) Japanese patients scheduled for various types of surgery (eg, cholecystectomy) were eligible. Patients were randomized to receive flurbiprofen axetil at 1 of 2 doses (25 or 50 mg, regardless of body weight) or inactive vehicle (saline), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by the infusion of the first 25% of calculated propofol dose (0.5 mg/kg at room temperature, 23 degrees C) into the largest dorsal vein of the hand through a 20-G IV cannula (without local anesthesia), followed by the release of the occlusion and delivery of propofol 2 mg/kg. An investigator blinded to treatment questioned each patient about pain intensity during propofol injection which was assessed using a verbal rating scale: 0 = none; 1 = mild; 2 = moderate; and 3 = severe. The overall prevalence of pain was calculated in each group. AEs at the injection site (pain, edema, wheal, inflammation) were assessed by the study investigator for 24 hours after surgery using spontaneous reporting and patient interview. A total of 150 patients, 75 young adults (38 men, 37

  3. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    SciTech Connect

    Chung, Eugene; Corbett, James R.; Moran, Jean M.; Griffith, Kent A.; Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L.; Ficaro, Edward C.; Pierce, Lori J.

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  4. Pharmacokinetics and tolerability (Study 1) with particular reference to ocular safety (Study 2) of tiotropium Respimat soft mist inhaler: findings from two dose-ranging studies in healthy men.

    PubMed

    Feifel, Ulrich; Wallenstein, Gudrun; Rominger, Karl-Ludwig; Trommeshauser, Dirk; Platz, Juliane

    2008-01-01

    Data are presented from two randomized, double-blind, placebo-controlled studies in which the tolerability of tiotropium Respimat Soft MistTM Inhaler (SMI), a new-generation, propellant-free device for use in COPD, and the ocular safety oftiotropium were examined. In Study 1, 36 healthy males received tiotropium 8, 16, or 32 microg (n = 9/dose) or placebo (n = 3/dose level), administered once daily via Respimat SMI for 14 days. Safety and pharmacokinetics were evaluated. In Study 2, 48 healthy males received tiotropium 0.02, 0.04, 0.08, 0.16, 0.28, or 0.40 microg (n = 6/dose) or placebo (n = 2/dose level), applied as two drops to one eye (the highest dose was a significant multiple of a percentage of the proposed Respimat SMI clinical dose that could be inadvertently deposited in the eye). Ocular parameters were measured over 24 hours. Tiotropium Respimat SMI at doses up to 32 microg was well tolerated in Study 1; typical dose-dependent anticholinergic adverse events of mild-to-moderate intensity were observed. In Study 2, ocular tiotropium administration did not affect pupil diameter, pupillary reflex, intraocular pressure, or accommodation. Tiotropium Respimat SMI was well tolerated. Inadvertent ocular exposure to tiotropium up to 0.40 g is unlikely to result in ocular adverse effects.

  5. Effects of Proton Radiation Dose, Dose Rate and Dose Fractionation on Hematopoietic Cells in Mice

    PubMed Central

    Ware, J. H.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X. S.; Rusek, A.; Kennedy, A. R.

    2012-01-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons. PMID:20726731

  6. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice.

    PubMed

    Ware, J H; Sanzari, J; Avery, S; Sayers, C; Krigsfeld, G; Nuth, M; Wan, X S; Rusek, A; Kennedy, A R

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  7. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    SciTech Connect

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  8. Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients: Model‐Based Support for Body Surface Area‐Based Dosing Over the 2‐ to 16‐Year Age Range

    PubMed Central

    Hanley, Michael J.; Mould, Diane R.; Taylor, Timothy J.; Gupta, Neeraj; Suryanarayan, Kaveri; Neuwirth, Rachel; Esseltine, Dixie‐Lee; Horton, Terzah M.; Aplenc, Richard; Alonzo, Todd A.; Lu, Xiaomin; Milton, Ashley

    2017-01-01

    Abstract This population analysis described the pharmacokinetics of bortezomib after twice‐weekly, repeat‐dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1.3 mg/m2 twice‐weekly, on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11 of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood samples were obtained and the plasma was harvested on day 8 over 0‐72 hours postdose to measure bortezomib concentrations by liquid chromatography‐tandem mass spectrometry. Concentration‐time data were analyzed by nonlinear mixed‐effects modeling. Covariates were examined using forward addition (P < .01)/backward elimination (P < .001). Data were included from 104 patients (49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2‐11 years/12‐16 years). Bortezomib pharmacokinetics were described by a 3‐compartment model with linear elimination. Body surface area adequately accounted for variability in clearance (exponent 0.97), supporting body surface area‐based dosing. Stratified visual predictive check simulations verified that neither age group nor patient population represented sources of meaningful pharmacokinetic heterogeneity not accounted for by the final population pharmacokinetic model. Following administration of 1.3 mg/m2 intravenous bortezomib doses, body surface area–normalized clearance in pediatric patients was similar to that observed in adult patients, thereby indicating that this dose achieves similar systemic exposures in pediatric patients. PMID:28419486

  9. Accelerated stability studies on 16-methylene-17 alpha-acetoxy-19-nor-pregn- 4-ene-3,20-dione (Nestorone).

    PubMed

    Ahmed, S M; Arcuri, F; Li, F; Moo-Young, A J; Monder, C

    1995-08-01

    The stability of the contraceptive steroid, Nestorone (16-methylene-17 alpha-acetoxy-19-nor-pregn-4-ene-3,20-dione) in the solid state and in aqueous solutions, was investigated using reverse-phase high-performance liquid chromatography. In the solid state, whether as a powder or when it is incorporated into Silastic implants, the steroid does not undergo detectable degradation even under severe experimental conditions. In solution, the drug undergoes slow degradation that is dependent on temperature and pH of the medium. The decomposition is defined by first-order mechanism. As expected, the reaction rate increases with increasing storage temperature. The linearity of the Arrhenius plot indicates that there is no change in the reaction mechanism within the temperature range studied. In alkaline media, the drug degrades at a faster rate through hydrolytic rather than an oxidative mechanism. The major hydrolytic degradation product, 16-methylene-17 alpha-hydroxy-19-nor-pregn-4-ene-3,20-dione, was separated and identified by mass spectrometry.

  10. A Phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age.

    PubMed

    August, Allison; Glenn, Gregory M; Kpamegan, Eloi; Hickman, Somia P; Jani, Dewal; Lu, Hanxin; Thomas, D Nigel; Wen, Judy; Piedra, Pedro A; Fries, Louis F

    2017-06-27

    Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules. Placebo, or vaccine with 60μg or 120μg RSV F protein and 0.2, 0.4, or 0.8mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18-35years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91. All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120μg RSV F protein and 0.4mg aluminum, but persistence through 91days was modestly (∼25%) superior following two doses of 60μg RSV F protein and 0.8mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p=0.009 overall) over the Day 0 through 90 period. RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120μg RSV F and 0.4mg aluminum, which achieved peak immune responses in 14days and sufficient persistence through 91days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686. Copyright © 2017 Novavax. Published by Elsevier Ltd.. All rights reserved.

  11. Dose Range Evaluation of Liposomal Nystatin and Comparisons with Amphotericin B and Amphotericin B Lipid Complex in Temporarily Neutropenic Mice Infected with an Isolate of Aspergillus fumigatus with Reduced Susceptibility to Amphotericin B

    PubMed Central

    Denning, David W.; Warn, Peter

    1999-01-01

    Using an isolate of Aspergillus fumigatus that is less susceptible in vivo to amphotericin B than most other isolates, we compared different doses of liposomal nystatin (L-nystatin), liposomal amphotericin B (L-amphotericin), and amphotericin B lipid complex (ABLC) with amphotericin B deoxycholate. Four experiments with intravenously infected neutropenic mice were conducted. A dose of L-nystatin at 10 mg/kg of body weight was toxic (the mice had fits or respiratory arrest). The optimal dosage of L-nystatin was 5 mg/kg daily on days 1, 2, 4, and 7 (90% survival). This was superior to L-amphotericin (5 mg/kg [P = 0.24] and 1 mg/kg [P < 0.0001]), ABLC (5 mg/kg [P = 0.014] and 1 mg/kg [P < 0.0001]), and amphotericin B deoxycholate (5 mg/kg [P = 0.008]). In terms of liver and kidney cultures, L-nystatin (5 mg/kg) was superior to all other regimens (P = 0.0032 and <0.0001, respectively). Higher doses of L-amphotericin (25 and 50 mg/kg) in one earlier experiment were more effective (100% survival) than 1 mg of L-amphotericin per kg and amphotericin deoxycholate (5 mg/kg) in terms of mortality and both liver and kidney culture results and to L-amphotericin (5 mg/kg) in terms of liver and kidney culture results only. ABLC (25 mg/kg) given daily for 7 days was superior to ABLC (50 mg/kg [P = 0.03]) but not to ABLC at 5 mg/kg or amphotericin B deoxycholate in terms of mortality, although it was in terms of liver and kidney culture results. No dose-response for amphotericin B (5 and 1 mg/kg) was demonstrable. In conclusion, in this stringent model, high doses of L-amphotericin and ABLC could overcome reduced susceptibility to amphotericin B deoxycholate, but all were inferior to 5- to 10-fold lower doses of L-nystatin. PMID:10543734

  12. GEA CRDA Range Data Analysis

    DTIC Science & Technology

    1999-07-28

    E1, July-August 1998 18 3.3. Example 3: SatMex, Solidaridad 2, May-June 1998 27 3.4. Example 4: PanAmSat, Galaxy IV, May-June 1998 33 3.5...17 Millstone measurements residuals for Telstar 401 on Days 181-263. 26 3-18 Millstone measurement residuals for Solidaridad 1 on Days 141-153...with 29 SatMex range data. 3-19 Hermosillo B-- Solidaridad 1 range residuals through Days 135-144 with bias 30 removed. 3-20 Iztapalapa D

  13. Passive Ranging

    DTIC Science & Technology

    1988-08-01

    1981). 5. R. Courant and D. Hilbert, Methods of Mathematical Physics , Vol. I, English ed., * Interscience, New York, 1953. 32 32 APPENDIX A CALCULATION...K Courant and D. Hilbert, Methods of Mathematical Physics , Vol. I, English ed., * Interscience, New York, 1953. A-8 APPENDIX B * RANGING ACCURACY IN

  14. A Phase I Study of Light Dose for Photodynamic Therapy (PDT) Using 2-[1-hexyloxyethyl]-2 devinyl Pyropheophorbide-a (HPPH) for Treatment of Non-small Cell Carcinoma in situ or Non-small Cell Microinvasive Bronchogenic Carcinoma. A Dose Ranging Study

    PubMed Central

    Dhillon, Samjot Singh; Demmy, Todd L.; Yendamuri, Sai; Loewen, Gregory; Nwogu, Chukwumere; Cooper, Michele; Henderson, Barbara W.

    2015-01-01

    Introduction We report a phase I trial of photodynamic therapy (PDT) of carcinoma-insitu (CIS) and microinvasive cancer (MIC) of the central airways with the photosensitizer (PS) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH). HPPH has the advantage of minimal general phototoxicity over the commonly used PS porfimer sodium (Photofrin®). Methods The objectives of this study were 1) to determine the maximally tolerated light dose at a fixed PS dose and 2) to gain initial insight into the effectiveness of this treatment approach. Seventeen patients with 21 CIS/MIC lesions were treated with HPPH with light dose escalation starting from 75 J/cm2 to 85, 95,125, and 150 J/cm2 respectively. Follow-up bronchoscopy for response assessment was done at one and six months, respectively. Results The rate of pathological complete response (CR) was 82.4% (14/17 evaluable lesions; 14 patients) at one-month and 72.7% (8/11 lesions; 8 patients) at 6 months. Only 4 patients developed mild skin erythema. One of the three patients in 150 J/cm2 light dose group experienced a serious adverse event. This patient had respiratory distress due to mucus plugging, which precipitated cardiac ischemia. Two additional patients treated subsequently at this light dose had no adverse events. The third sixth patient in this dose group was not recruited and the study was terminated because of delays in HPPH supply. However, given the observed serious adverse event, it is recommended that the light dose not exceed 125J/cm2. Conclusions PDT with HPPH can be safely used for the treatment of CIS/MIC of the airways, with potential effectiveness comparable to that reported for porfimer sodium in earlier studies. PMID:26718878

  15. Phase 2, Randomized, Double-Blind, Dose-Ranging Study Evaluating the Safety, Tolerability, Population Pharmacokinetics, and Efficacy of Oral Torezolid Phosphate in Patients with Complicated Skin and Skin Structure Infections▿ † ‡

    PubMed Central

    Prokocimer, P.; Bien, P.; Surber, J.; Mehra, P.; DeAnda, C.; Bulitta, J. B.; Corey, G. R.

    2011-01-01

    Torezolid (TR-700) is the active moiety of the prodrug torezolid phosphate ([TP] TR-701), a second-generation oxazolidinone with 4- to 16-fold greater potency than linezolid against Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind phase 2 study evaluated three levels (200, 300, or 400 mg) of oral, once-daily TP over 5 to 7 days for complicated skin and skin structure infections (cSSSI). Patients 18 to 75 years old with cSSSI caused by suspected or confirmed Gram-positive pathogens were randomized 1:1:1. Of 188 treated patients, 76.6% had abscesses, 17.6% had extensive cellulitis, and 5.9% had wound infections. S. aureus, the most common pathogen, was isolated in 90.3% of patients (139/154) with a baseline pathogen; 80.6% were MRSA. Cure rates in clinically evaluable patients were 98.2% at 200 mg, 94.4% at 300 mg, and 94.4% at 400 mg. Cure rates were consistent across diagnoses, regardless of lesion size or the presence of systemic signs of infection. Clinical cure rates in patients with S. aureus isolated at baseline were 96.6% overall and 96.8% for MRSA. TP was safe and well tolerated at all dose levels. No patients discontinued treatment due to an adverse event. Three-stage hierarchical population pharmacokinetic modeling yielded a geometric mean clearance of 8.28 liters/h (between-patient variability, 32.3%), a volume of the central compartment of 71.4 liters (24.0%), and a volume of the peripheral compartment of 27.9 liters (35.7%). Results of this study show a high degree of efficacy at all three dose levels without significant differences in the safety profile and support the continued evaluation of TP for the treatment of cSSSI in phase 3 trials. PMID:21115795

  16. Range and range rate system

    NASA Technical Reports Server (NTRS)

    Graham, Olin L. (Inventor); Russell, Jim K. (Inventor); Epperly, Walter L. (Inventor)

    1988-01-01

    A video controlled solid state range finding system which requires no radar, high power laser, or sophisticated laser target is disclosed. The effective range of the system is from 1 to about 200 ft. The system includes an opto-electric camera such as a lens CCD array device. A helium neon laser produces a source beam of coherent light which is applied to a beam splitter. The beam splitter applies a reference beam to the camera and produces an outgoing beam applied to a first angularly variable reflector which directs the outgoing beam to the distant object. An incoming beam is reflected from the object to a second angularly variable reflector which reflects the incoming beam to the opto-electric camera via the beam splitter. The first reflector and the second reflector are configured so that the distance travelled by the outgoing beam from the beam splitter and the first reflector is the same as the distance travelled by the incoming beam from the second reflector to the beam splitter. The reference beam produces a reference signal in the geometric center of the camera. The incoming beam produces an object signal at the camera.

  17. The intravenous to oral relative milligram potency ratio of morphine during chronic dosing in cancer pain.

    PubMed

    Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Sarhill, Nabeel; Rivera, Nilo; Davis, Mellar; Lagman, Ruth; Legrand, Susan

    2010-01-01

    Morphine (M) is the opioid analgesic of choice for severe cancer pain. The IV to PO M equipotent switch ratio (CR) is controversial. We designed this prospective observational cohort to confirm the efficacy and safety of M IV to PO CR of 1:3. Consecutive cancer patients admitted to an inpatient palliative medicine unit were screened for inclusion. Pain was managed by palliative medicine specialists. They were blinded to the patient data collected, and the calculated CR. The switch was considered successful if the following criteria were met: (1) Pain adequately controlled: pain rated as none or mild (2) Number of RD less than 4 (for non incident pain) per 24 hours (3) No limiting side effects. We used Day 3 ATC M dose for CR calculations. The major outcome measures were the IV : PO CR ratio, morphine doses (mg/day), pain severity, number of PRN doses, and day 1 and day 3side effects. Descriptive statistics were used to report mean, median, standard deviation and range of different variables. Two hundred and fifty six consecutive admissions were screened, and 106 were eligible for the study. Sixty two underwent a successful M route switch and were included in this analysis. A ratio of 1:3 was safely implemented over a wide M dose range. About 80% were successfully switched with a calculated CR of 1:3. 20% required an oral M dose adjustment after route switch either to better pain control or reduce side effects with a resultant higher (e.g. 1:4) or lower (e.g. 1:2) calculated potency ratios respectively. A potency ratio of 1:3 was safe as evaluated by common M side-effects, the dose also easy to calculate. The 1: 3 M IV to PO relative milligram potency ratio appears correct and practical for most patients over a wide M dose range.

  18. Tribological Behavior of Plasma-Sprayed Al2O3-20 wt.%TiO2 Coating

    NASA Astrophysics Data System (ADS)

    Cui, Shiyu; Miao, Qiang; Liang, Wenping; Zhang, Zhigang; Xu, Yi; Ren, Beilei

    2017-05-01

    Al2O3-20 wt.% TiO2 ceramic coatings were deposited on the surface of Grade D steel by plasma spraying of commercially available powders. The phases and the microstructures of the coatings were investigated by x-ray diffraction and scanning electron microscopy, respectively. The Al2O3-20 wt.% TiO2 composite coating exhibited a typical inter-lamellar structure consisting of the γ-Al2O3 and the Al2TiO5 phases. The dry sliding wear behavior of the coating was examined at 20 °C using a ball-on-disk wear tester. The plasma-sprayed coating showed a low wear rate ( 4.5 × 10-6 mm3 N-1 m-1), which was <2% of that of the matrix ( 283.3 × 10-6 mm3 N-1 m-1), under a load of 15 N. In addition, the tribological behavior of the plasma-sprayed coating was analyzed by examining the microstructure after the wear tests. It was found that delamination of the Al2TiO5 phase was the main cause of the wear during the sliding wear tests. A suitable model was used to simulate the wear mechanism of the coating.

  19. A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers

    PubMed Central

    Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion

    2012-01-01

    As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted.   This study is registered at www.clinicaltrials.gov NCT number: NCT01106092 PMID:22330958

  20. A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers.

    PubMed

    Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion

    2012-03-01

    As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092.

  1. Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix

    SciTech Connect

    Akine, Y.; Tokita, N.; Ogino, T.; Kajiura, Y.; Tsukiyama, I.; Egawa, S. )

    1990-12-01

    By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

  2. Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections.

    PubMed

    Sims, Matthew; Mariyanovski, Valeri; McLeroth, Patrick; Akers, Wayne; Lee, Yu-Chieh; Brown, Michelle L; Du, Jiejun; Pedley, Alison; Kartsonis, Nicholas A; Paschke, Amanda

    2017-09-01

    The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem non-susceptible pathogens. To explore relebactam's safety, tolerability and efficacy, we conducted a randomized (1:1:1), controlled, Phase 2 trial comparing imipenem/cilastatin+relebactam 250 mg, imipenem/cilastatin+relebactam 125 mg and imipenem/cilastatin alone in adults with complicated urinary tract infections (cUTI) or acute pyelonephritis, regardless of baseline pathogen susceptibility. Treatment was administered intravenously every 6 h for 4-14 days, with optional step-down to oral ciprofloxacin. The primary endpoint was favourable microbiological response rate (pathogen eradication) at discontinuation of intravenous therapy (DCIV) in the microbiologically evaluable (ME) population. Non-inferiority of imipenem/cilastatin+relebactam over imipenem/cilastatin alone was defined as lower bounds of the 95% CI for treatment differences being above -15%. At DCIV, 71 patients in the imipenem/cilastatin + 250 mg relebactam, 79 in the imipenem/cilastatin + 125 mg relebactam and 80 in the imipenem/cilastatin-only group were ME; 51.7% had cUTI and 48.3% acute pyelonephritis. Microbiological response rates were 95.5%, 98.6% and 98.7%, respectively, confirming non-inferiority of both imipenem/cilastatin + relebactam doses to imipenem/cilastatin alone. Clinical response rates were 97.1%, 98.7% and 98.8%, respectively. All 23 ME patients with imipenem non-susceptible pathogens had favourable DCIV microbiological responses (100% in each group). Among all 298 patients treated, 28.3%, 29.3% and 30.0% of patients, respectively, had treatment-emergent adverse events. The most common treatment-related adverse events across groups (1.0%-4.0%) were diarrhoea, nausea and headache. Imipenem/cilastatin + relebactam (250 or 125 mg) was as effective as imipenem/cilastatin alone for treatment of cUTI. Both relebactam-containing regimens were well tolerated. (NCT01505634).

  3. Dose rate mapping of VMAT treatments

    NASA Astrophysics Data System (ADS)

    Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

    2016-06-01

    Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

  4. Dose rate mapping of VMAT treatments.

    PubMed

    Podesta, Mark; Popescu, I Antoniu; Verhaegen, Frank

    2016-06-07

    Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min(-1) and 12 Gy min(-1) but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min(-1). Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

  5. Fabrication of Al{sub 2}O{sub 3}-20 vol.% Al nanocomposite powders using high energy milling and their sinterability

    SciTech Connect

    Zawrah, M.F.; Abdel-kader, H.; Elbaly, N.E.

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer Al{sub 2}O{sub 3}/Al nanocomposite powders were prepared via high energy ball milling. After 20 h milling, the size of Al{sub 2}O{sub 3}-20 vol.% Al nanocomposite particles was in the range of 23-29 nm. A uniform distribution of nanosized Al reinforcement throughout the Al{sub 2}O{sub 3} matrix, coating the particles was successfully obtained. Black-Right-Pointing-Pointer There was no any sign of phase changes during the milling. A competition between the cold welding mechanism and the fracturing mechanism were found during milling and finally the above two mechanisms reached an equilibrium. Black-Right-Pointing-Pointer The highest value of relative density was obtained for the sintered bodies at 1500 Degree-Sign C. Black-Right-Pointing-Pointer The harness of the sintered composite was decreased while the fracture toughness was improved after addition Al into alumina. -- Abstract: In this study, alumina-based matrix nanocomposite powders reinforced with Al particles were fabricated and investigated. The sinterability of the prepared nanocomposite powder at different firing temperature was also conducted. Their mechanical properties in terms of hardness and toughness were tested. Alumina and aluminum powder mixtures were milled in a planetary ball mill for various times up to 30 h in order to produce Al{sub 2}O{sub 3}-20% Al nanocomposite. The phase composition, morphological and microstructural changes during mechanical milling of the nanocomposite particles were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM) techniques, respectively. The crystallite size and internal strain were evaluated by XRD patterns using Scherrer methods. A uniform distribution of the Al reinforcement in the Al{sub 2}O{sub 3} matrix was successfully obtained after milling the powders. The results revealed that there was no any sign of phase changes during the milling. The crystal

  6. Radiation dose in dental radiology.

    PubMed

    Cohnen, M; Kemper, J; Möbes, O; Pawelzik, J; Mödder, U

    2002-03-01

    The aim of this study was to compare radiation exposure in panoramic radiography (PR), dental CT, and digital volume tomography (DVT). An anthropomorphic Alderson-Rando phantom and two anatomical head phantoms with thermoluminescent dosimeters fixed at appropriate locations were exposed as in a dental examination. In PR and DVT, standard parameters were used while variables in CT included mA, pitch, and rotation time. Image noise was assessed in dental CT and DVT. Radiation doses to the skin and internal organs within the primary beam and resulting from scatter radiation were measured and expressed as maximum doses in mGy. For PR, DVT, and CT, these maximum doses were 0.65, 4.2, and 23 mGy. In dose-reduced CT protocols, radiation doses ranged from 10.9 to 6.1 mGy. Effective doses calculated on this basis showed values below 0.1 mSv for PR, DVT, and dose-reduced CT. Image noise was similar in DVT and low-dose CT. As radiation exposure and image noise of DVT is similar to low-dose CT, this imaging technique cannot be recommended as a general alternative to replace PR in dental radiology.

  7. Experimental evaluation of neutron dose in radiotherapy patients: Which dose?

    SciTech Connect

    Romero-Expósito, M. Domingo, C.; Ortega-Gelabert, O.; Gallego, S.; Sánchez-Doblado, F.

    2016-01-15

    Purpose: The evaluation of peripheral dose has become a relevant issue recently, in particular, the contribution of secondary neutrons. However, after the revision of the Recommendations of the International Commission on Radiological Protection, there has been a lack of experimental procedure for its evaluation. Specifically, the problem comes from the replacement of organ dose equivalent by the organ-equivalent dose, being the latter “immeasurable” by definition. Therefore, dose equivalent has to be still used although it needs the calculation of the radiation quality factor Q, which depends on the unrestricted linear energy transfer, for the specific neutron irradiation conditions. On the other hand, equivalent dose is computed through the radiation weighting factor w{sub R}, which can be easily calculated using the continuous function provided by the recommendations. The aim of the paper is to compare the dose equivalent evaluated following the definition, that is, using Q, with the values obtained by replacing the quality factor with w{sub R}. Methods: Dose equivalents were estimated in selected points inside a phantom. Two types of medical environments were chosen for the irradiations: a photon- and a proton-therapy facility. For the estimation of dose equivalent, a poly-allyl-diglicol-carbonate-based neutron dosimeter was used for neutron fluence measurements and, additionally, Monte Carlo simulations were performed to obtain the energy spectrum of the fluence in each point. Results: The main contribution to dose equivalent comes from neutrons with energy higher than 0.1 MeV, even when they represent the smallest contribution in fluence. For this range of energy, the radiation quality factor and the radiation weighting factor are approximately equal. Then, dose equivalents evaluated using both factors are compatible, with differences below 12%. Conclusions: Quality factor can be replaced by the radiation weighting factor in the evaluation of dose

  8. Experimental evaluation of neutron dose in radiotherapy patients: Which dose?

    PubMed

    Romero-Expósito, M; Domingo, C; Sánchez-Doblado, F; Ortega-Gelabert, O; Gallego, S

    2016-01-01

    The evaluation of peripheral dose has become a relevant issue recently, in particular, the contribution of secondary neutrons. However, after the revision of the Recommendations of the International Commission on Radiological Protection, there has been a lack of experimental procedure for its evaluation. Specifically, the problem comes from the replacement of organ dose equivalent by the organ-equivalent dose, being the latter "immeasurable" by definition. Therefore, dose equivalent has to be still used although it needs the calculation of the radiation quality factor Q, which depends on the unrestricted linear energy transfer, for the specific neutron irradiation conditions. On the other hand, equivalent dose is computed through the radiation weighting factor wR, which can be easily calculated using the continuous function provided by the recommendations. The aim of the paper is to compare the dose equivalent evaluated following the definition, that is, using Q, with the values obtained by replacing the quality factor with wR. Dose equivalents were estimated in selected points inside a phantom. Two types of medical environments were chosen for the irradiations: a photon- and a proton-therapy facility. For the estimation of dose equivalent, a poly-allyl-diglicol-carbonate-based neutron dosimeter was used for neutron fluence measurements and, additionally, Monte Carlo simulations were performed to obtain the energy spectrum of the fluence in each point. The main contribution to dose equivalent comes from neutrons with energy higher than 0.1 MeV, even when they represent the smallest contribution in fluence. For this range of energy, the radiation quality factor and the radiation weighting factor are approximately equal. Then, dose equivalents evaluated using both factors are compatible, with differences below 12%. Quality factor can be replaced by the radiation weighting factor in the evaluation of dose equivalent in radiotherapy environments simplifying the

  9. Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents

    PubMed Central

    Chatelut, E; White-Koning, M L; Mathijssen, R HJ; Puisset, F; Baker, S D; Sparreboom, A

    2012-01-01

    Background: Dose banding is a recently suggested dosing method that uses predefined ranges (bands) of body surface area (BSA) to calculate each patient's dose by using a single BSA-value per band. Thus, drugs with sufficient long-term stability can be prepared in advance. The main advantages of dose banding are to reduce patient waiting time and improve pharmacy capacity planning; additional benefits include reduced medication errors, reduced drug wastage, and prospective quality control. This study compares dose banding with individual BSA dosing and fixed dose according to pharmacokinetic criteria. Methods: Three BSA bands were defined: BSA<1.7 m2, 1.7 m2⩽BSA<1.9 m2, BSA⩾1.9 m2 and each patient dose was calculated based on a unique BSA-value per band (1.55, 1.80, and 2.05 m2, respectively). By using individual clearance values of six drugs (cisplatin, docetaxel, paclitaxel, doxorubicin, irinotecan, and topotecan) from 1012 adult cancer patients in total, the AUCs corresponding to three dosing methods (BSA dosing, dose banding, and fixed dose) were compared with a target AUC for each drug. Results: For all six drugs, the per cent variation in individual dose obtained with dose banding compared with BSA dosing ranged between −14% and +22%, and distribution of AUC values was very similar with both dosing methods. In terms of reaching the target AUC, there was no significant difference in precision between dose banding and BSA dosing, except for paclitaxel (32.0% vs 30.7%, respectively; P<0.05). However, precision was significantly better for BSA dosing compared with fixed dose for four out of six drugs. Conclusion: For the studied drugs, implementation of dose banding should be considered as it entails no significant increase in interindividual plasma exposure. PMID:22929884

  10. Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents.

    PubMed

    Chatelut, E; White-Koning, M L; Mathijssen, R Hj; Puisset, F; Baker, S D; Sparreboom, A

    2012-09-25

    Dose banding is a recently suggested dosing method that uses predefined ranges (bands) of body surface area (BSA) to calculate each patient's dose by using a single BSA-value per band. Thus, drugs with sufficient long-term stability can be prepared in advance. The main advantages of dose banding are to reduce patient waiting time and improve pharmacy capacity planning; additional benefits include reduced medication errors, reduced drug wastage, and prospective quality control. This study compares dose banding with individual BSA dosing and fixed dose according to pharmacokinetic criteria. Three BSA bands were defined: BSA<1.7 m(2), 1.7 m(2)≤ BSA<1.9 m(2), BSA ≥ 1.9 m(2) and each patient dose was calculated based on a unique BSA-value per band (1.55, 1.80, and 2.05 m(2), respectively). By using individual clearance values of six drugs (cisplatin, docetaxel, paclitaxel, doxorubicin, irinotecan, and topotecan) from 1012 adult cancer patients in total, the AUCs corresponding to three dosing methods (BSA dosing, dose banding, and fixed dose) were compared with a target AUC for each drug. For all six drugs, the per cent variation in individual dose obtained with dose banding compared with BSA dosing ranged between -14% and +22%, and distribution of AUC values was very similar with both dosing methods. In terms of reaching the target AUC, there was no significant difference in precision between dose banding and BSA dosing, except for paclitaxel (32.0% vs 30.7%, respectively; P<0.05). However, precision was significantly better for BSA dosing compared with fixed dose for four out of six drugs. For the studied drugs, implementation of dose banding should be considered as it entails no significant increase in interindividual plasma exposure.

  11. High-dose fenretinide in oral leukoplakia.

    PubMed

    William, William N; Lee, J Jack; Lippman, Scott M; Martin, Jack W; Chakravarti, Nitin; Tran, Hai T; Sabichi, Anita L; Kim, Edward S; Feng, Lei; Lotan, Reuben; Papadimitrakopoulou, Vassiliki A

    2009-01-01

    We previously showed that low-dose fenretinide (200 mg/d) had limited activity in retinoid-resistant oral leukoplakia (34% response rate) possibly because serum drug levels were insufficient to induce retinoid receptor-independent apoptosis. Therefore, we designed the single-arm phase II trial reported here to investigate whether higher-dose fenretinide would improve leukoplakia response over that of our previous study. Leukoplakia patients received fenretinide (900 mg/m(2) twice daily) in four 3-week cycles (1 week on drug followed by 2 weeks off). At week 12, clinical responses were determined and blood samples were collected for serum drug level assessments. A planned interim futility analysis led to early trial closure after the initial 15 (of 25 planned) patients because only 3 (20%) had a partial response (stopping rule: dose fenretinide inhibited the growth of head and neck cancer cells more and oral leukoplakia cells less than did lower doses of fenretinide. This result is consistent with our clinical finding that high-dose fenretinide did not improve on the historical response rate of lower-dose fenretinide in our previous oral leukoplakia trial.

  12. Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

    PubMed

    Pushpakom, Sudeep P; Taylor, Claire; Kolamunnage-Dona, Ruwanthi; Spowart, Catherine; Vora, Jiten; García-Fiñana, Marta; Kemp, Graham J; Whitehead, John; Jaki, Thomas; Khoo, Saye; Williamson, Paula; Pirmohamed, Munir

    2015-10-15

    Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy. This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm. The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West-Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement. 04196/0024/001-0001; 2012-000935-18; 51069819. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  13. Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy

    PubMed Central

    Pushpakom, Sudeep P; Taylor, Claire; Kolamunnage-Dona, Ruwanthi; Spowart, Catherine; Vora, Jiten; García-Fiñana, Marta; Kemp, Graham J; Whitehead, John; Jaki, Thomas; Khoo, Saye; Williamson, Paula; Pirmohamed, Munir

    2015-01-01

    Introduction Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy. Methods and analysis This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment—Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm. Ethics and dissemination The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West—Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement. Trial registration numbers 04196/0024/001-0001; EUDRACT: 2012

  14. Acoustic dose and acoustic dose-rate.

    PubMed

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  15. Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

    PubMed

    Madas, Balázs G

    2016-07-01

    Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

  16. Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose

    NASA Technical Reports Server (NTRS)

    Welton, Andrew; Lee, Kerry

    2010-01-01

    While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.

  17. Estimating thyroid dose in pediatric CT exams from surface dose measurement

    NASA Astrophysics Data System (ADS)

    Al-Senan, Rani; Mueller, Deborah L.; Hatab, Mustapha R.

    2012-07-01

    The purpose of this study was to investigate the possibility of estimating pediatric thyroid doses from CT using surface neck doses. Optically stimulated luminescence dosimeters were used to measure the neck surface dose of 25 children ranging in ages between one and three years old. The neck circumference for each child was measured. The relationship between obtained surface doses and thyroid dose was studied using acrylic phantoms of various sizes and with holes of different depths. The ratios of hole-to-surface doses were used to convert patients' surface dose to thyroid dose. ImPACT software was utilized to calculate thyroid dose after applying the appropriate age correction factors. A paired t-test was performed to compare thyroid doses from our approach and ImPACT. The ratio of thyroid to surface dose was found to be 1.1. Thyroid doses ranged from 20 to 80 mGy. Comparison showed no statistical significance (p = 0.18). In addition, the average of surface dose variation along the z-axis in helical scans was studied and found to range between 5% (in 10 cm diameter phantom/24 mm collimation/pitch 1.0) and 8% (in 16 cm diameter phantom/12 mm collimation/pitch 0.7). We conclude that surface dose is an acceptable predictor for pediatric thyroid dose from CT. The uncertainty due to surface dose variability may be reduced if narrower collimation is used with a pitch factor close to 1.0. Also, the results did not show any effect of thyroid depth on the measured dose.

  18. Weldon Spring historical dose estimate

    SciTech Connect

    Meshkov, N.; Benioff, P.; Wang, J.; Yuan, Y.

    1986-07-01

    This study was conducted to determine the estimated radiation doses that individuals in five nearby population groups and the general population in the surrounding area may have received as a consequence of activities at a uranium processing plant in Weldon Spring, Missouri. The study is retrospective and encompasses plant operations (1957-1966), cleanup (1967-1969), and maintenance (1969-1982). The dose estimates for members of the nearby population groups are as follows. Of the three periods considered, the largest doses to the general population in the surrounding area would have occurred during the plant operations period (1957-1966). Dose estimates for the cleanup (1967-1969) and maintenance (1969-1982) periods are negligible in comparison. Based on the monitoring data, if there was a person residing continually in a dwelling 1.2 km (0.75 mi) north of the plant, this person is estimated to have received an average of about 96 mrem/yr (ranging from 50 to 160 mrem/yr) above background during plant operations, whereas the dose to a nearby resident during later years is estimated to have been about 0.4 mrem/yr during cleanup and about 0.2 mrem/yr during the maintenance period. These values may be compared with the background dose in Missouri of 120 mrem/yr.

  19. Synthesis of nonionic-anionic colloidal systems based on alkaline and ammonium β-nonylphenol polyethyleneoxy (n = 3-20) propionates/dodecylbenzenesulfonates with prospects for food hygiene.

    PubMed

    Jianu, Calin

    2012-09-08

    The main objective of this work was to obtain a binary system of surface-active components (nonionic soap - alkaline and/or ammonium dodecylbenzenesulfonate) with potential competences in food hygiene, by accessing a scheme of classical reactions (cyanoethylation, total acid hydrolysis and stoichiometric neutralization with inorganic alkaline and/or organic ammonium bases) adapted to heterogeneously polyethoxylated nonylphenols (n = 3-20). In the processing system mentioned, dodecylbenzenesulfonic acid, initially the acid catalyst for the exhaustive hydrolysis of β-nonylphenolpolyethyleneoxy (n = 3-20) propionitriles, becomes together with the nonionic soap formed the second surface-active component of the binary system. In the reaction scheme adopted the influence of the main operating (duration, temperature, molar ratio of reagents) and structural parameters (degree of oligomerization of the polyoxyethylene chain) on the processing yields for the synthetic steps was followed. The favorable role of the polyoxyethylene chain size is remarked, through its specific conformation and its alkaline cations sequestration competences on the yields of cyanoethylation, but also the beneficial influence of phase-transfer catalysts in the total acid hydrolysis step. The chemical stability of dodecylbenzenesulfonic acid (DBSH) at the temperature and strongly acidic pH of the reaction environment is confirmed. The controlled change of the amount of DBSH in the final binary system will later confer it potential colloidal competences in food hygiene receipts. The preliminary synthetic tests performed confirmed the prospect of obtaining a broad range of useful colloidal competences in various food hygiene scenarios.

  20. Peripheral doses from pediatric IMRT

    SciTech Connect

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-07-15

    Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged

  1. Calculation of dose conversion factors for doses in the fingernails to organ doses at external gamma irradiation in air

    PubMed Central

    Khailov, A.M.; Ivannikov, A. I.; Skvortsov, V.G.; Stepanenko, V.F.; Orlenko, S.P.; Flood, A.B.; Williams, B.B.; Swartz, H.M.

    2015-01-01

    Absorbed doses to fingernails and organs were calculated for a set of homogenous external gamma-ray irradiation geometries in air. The doses were obtained by stochastic modeling of the ionizing particle transport (Monte Carlo method) for a mathematical human phantom with arms and hands placed loosely along the sides of the body. The resulting dose conversion factors for absorbed doses in fingernails can be used to assess the dose distribution and magnitude in practical dose reconstruction problems. For purposes of estimating dose in a large population exposed to radiation in order to triage people for treatment of acute radiation syndrome, the calculated data for a range of energies having a width of from 0.05 to 3.5 MeV were used to convert absorbed doses in fingernails to corresponding doses in organs and the whole body as well as the effective dose. Doses were assessed based on assumed rates of radioactive fallout at different time periods following a nuclear explosion. PMID:26347593

  2. Can digoxin dose requirements be predicted?

    PubMed

    Dobbs, S M; Mawer, G E; Rodgers, M; Woodcock, B G; Lucas, S B

    1976-04-01

    A search for patient variables relevant to digoxin dose requirements was made in fourty-three patients with a wide range of renal and hepatic function. The daily dose of digoxin to achieve a mean serum concentration of 1.5 ng/ml, the standardized dose, was calculated for each patient. The standardized dose correlated significantly with the following variables, in descending order of correlation coefficient; creatinine clearance, serum creatinine concentration, body weight and serum albumin concentration. An equation containing the two independent variables, creatinine clearance and serum albumin concentration, had a significantly stronger correlation with standardized dose than creatinine clearance alone. Attempts were made in each patient to predict the standardized dose using both empirical prescribing methods and the published nomograms. Although a maximum of 70% of the variance of the standardized dose was explained, this corresponded approximately to one patient in three having a predicted dose outside the 95% confidnece limits for the standardized dose. There remain important sources of individual variation in digoxin dose requirements yet to be identified. Future application of empirical prescribing methods, such as multiple linear regression and Bayes' theorem, to prescription for large, defined patient groups may improve dose prediction for individual patients.

  3. Can digoxin dose requirements be predicted?

    PubMed Central

    Dobbs, S M; Mawer, G E; Rodgers, M; Woodcock, B G; Lucas, S B

    1976-01-01

    A search for patient variables relevant to digoxin dose requirements was made in fourty-three patients with a wide range of renal and hepatic function. The daily dose of digoxin to achieve a mean serum concentration of 1.5 ng/ml, the standardized dose, was calculated for each patient. The standardized dose correlated significantly with the following variables, in descending order of correlation coefficient; creatinine clearance, serum creatinine concentration, body weight and serum albumin concentration. An equation containing the two independent variables, creatinine clearance and serum albumin concentration, had a significantly stronger correlation with standardized dose than creatinine clearance alone. Attempts were made in each patient to predict the standardized dose using both empirical prescribing methods and the published nomograms. Although a maximum of 70% of the variance of the standardized dose was explained, this corresponded approximately to one patient in three having a predicted dose outside the 95% confidnece limits for the standardized dose. There remain important sources of individual variation in digoxin dose requirements yet to be identified. Future application of empirical prescribing methods, such as multiple linear regression and Bayes' theorem, to prescription for large, defined patient groups may improve dose prediction for individual patients. PMID:973957

  4. Dose optimization tool

    NASA Astrophysics Data System (ADS)

    Amir, Ornit; Braunstein, David; Altman, Ami

    2003-05-01

    A dose optimization tool for CT scanners is presented using patient raw data to calculate noise. The tool uses a single patient image which is modified for various lower doses. Dose optimization is carried out without extra measurements by interactively visualizing the dose-induced changes in this image. This tool can be used either off line, on existing image(s) or, as a pre - requisite for dose optimization for the specific patient, during the patient clinical study. The algorithm of low-dose simulation consists of reconstruction of two images from a single measurement and uses those images to create the various lower dose images. This algorithm enables fast simulation of various low dose (mAs) images on a real patient image.

  5. Dose Response Data for Hormonally Active Chemicals ...

    EPA Pesticide Factsheets

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

  6. DICOM organ dose does not accurately represent calculated dose in mammography

    NASA Astrophysics Data System (ADS)

    Suleiman, Moayyad E.; Brennan, Patrick C.; McEntee, Mark F.

    2016-03-01

    This study aims to analyze the agreement between the mean glandular dose estimated by the mammography unit (organ dose) and mean glandular dose calculated using Dance et al published method (calculated dose). Anonymised digital mammograms from 50 BreastScreen NSW centers were downloaded and exposure information required for the calculation of dose was extracted from the DICOM header along with the organ dose estimated by the system. Data from quality assurance annual tests for the included centers were collected and used to calculate the mean glandular dose for each mammogram. Bland-Altman analysis and a two-tailed paired t-test were used to study the agreement between calculated and organ dose and the significance of any differences. A total of 27,869 dose points from 40 centers were included in the study, mean calculated dose and mean organ dose (+/- standard deviation) were 1.47 (+/-0.66) and 1.38 (+/-0.56) mGy respectively. A statistically significant 0.09 mGy bias (t = 69.25; p<0.0001) with 95% limits of agreement between calculated and organ doses ranging from -0.34 and 0.52 were shown by Bland-Altman analysis, which indicates a small yet highly significant difference between the two means. The use of organ dose for dose audits is done at the risk of over or underestimating the calculated dose, hence, further work is needed to identify the causal agents for differences between organ and calculated doses and to generate a correction factor for organ dose.

  7. Elucidating the role of dose in the biopharmaceutics classification of drugs: the concepts of critical dose, effective in vivo solubility, and dose-dependent BCS.

    PubMed

    Charkoftaki, Georgia; Dokoumetzidis, Aristides; Valsami, Georgia; Macheras, Panos

    2012-11-01

    To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose for the various classes of BCS and the marginal cases in between classes. Simulations based on the mathematical model of F versus dose produced patterns of a constant F throughout a wide range of doses for drugs of Classes I, II and III, justifying biowaiver claim. For Classes I and III the pattern of a constant F stops at a critical dose Dose(cr) after which the amount of drug absorbed, is independent from the dose. For doses higher than Dose(cr), Class I drugs become Class II and Class III drugs become Class IV. Dose(cr) was used to define an in vivo effective solubility as S(eff) = Dose(cr)/250 ml. Literature data were used to support our simulation results. A new biopharmaceutic classification of drugs is proposed, based on F, separating drugs into three regions, taking into account the dose, and Dose(cr), while the regions for claiming biowaiver are clearly defined.

  8. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

    PubMed Central

    Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

    2012-01-01

    For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

  9. There is no safe dose of prions.

    PubMed

    Fryer, Helen R; McLean, Angela R

    2011-01-01

    Understanding the circumstances under which exposure to transmissible spongiform encephalopathies (TSEs) leads to infection is important for managing risks to public health. Based upon ideas in toxicology and radiology, it is plausible that exposure to harmful agents, including TSEs, is completely safe if the dose is low enough. However, the existence of a threshold, below which infection probability is zero has never been demonstrated experimentally. Here we explore this question by combining data and mathematical models that describe scrapie infections in mice following experimental challenge over a broad range of doses. We analyse data from 4338 mice inoculated at doses ranging over ten orders of magnitude. These data are compared to results from a within-host model in which prions accumulate according to a stochastic birth-death process. Crucially, this model assumes no threshold on the dose required for infection. Our data reveal that infection is possible at the very low dose of a 1000 fold dilution of the dose that infects half the challenged animals (ID50). Furthermore, the dose response curve closely matches that predicted by the model. These findings imply that there is no safe dose of prions and that assessments of the risk from low dose exposure are right to assume a linear relationship between dose and probability of infection. We also refine two common perceptions about TSE incubation periods: that their mean values decrease linearly with logarithmic decreases in dose and that they are highly reproducible between hosts. The model and data both show that the linear decrease in incubation period holds only for doses above the ID50. Furthermore, variability in incubation periods is greater than predicted by the model, not smaller. This result poses new questions about the sources of variability in prion incubation periods. It also provides insight into the limitations of the incubation period assay.

  10. Range uncertainty in proton therapy due to variable biological effectiveness

    NASA Astrophysics Data System (ADS)

    Carabe, Alejandro; Moteabbed, Maryam; Depauw, Nicolas; Schuemann, Jan; Paganetti, Harald

    2012-03-01

    Traditionally, dose in proton radiotherapy is prescribed as Gy(RBE) by scaling up the physical dose by 10%. The relative biological effectiveness (RBE) of protons is considered to vary with dose-averaged linear energy transfer (LETd), dose (d) and (α/β)x. The increase of RBE with depth causes a shift of the falloff of the beam, i.e. a change of the beam range. The magnitude of this shift will depend on dose and (α/β)x. The aim of this project was to quantify the dependence of the range shift on these parameters. Three double-scattered beams of different ranges incident on a computational phantom consisting of different regions of interest (ROIs) were used. Each ROI was assigned with (α/β)x values between 0.5 and 20 Gy. The distribution of LETd within each ROI was obtained from a Monte Carlo simulation. The LETd distribution depends on the beam energy and thus its nominal range. The RBE values within the ROIs were calculated for doses between 1 and 15 Gy using an in-house developed biophysical model. Dose-volume histograms of the RBE-weighted doses were extracted for each ROI for a ‘fixed RBE’ (RBE = 1.1) and a ‘variable RBE’ (RBE = f (d, α/β, LETd)), and the percentage difference in range was obtained from the difference of the percentage volumes at the distal 80% of the dose. Range differences in normal tissue ((α/β)x = 3 Gy) of the order of 3-2 mm were obtained, respectively, for a shallow (physical range 4.8 cm) and a deep (physical range 12.8 cm) beam, when a dose of 1 Gy normalized to the mid-SOBP was delivered. As the dose increased to 15 Gy, the variable RBE decreases below 1.1 which induces ranges of about 1 mm shorter than those obtained with an RBE of 1.1. The shift in the range of an SOBP when comparing biological dose distributions obtained with a fixed or a variable RBE was quantified as a function of dose, (α/β)x and physical range (as a surrogate of the initial beam energy). The shift increases with the physical range but

  11. [Absorbed doses in dental radiology].

    PubMed

    Bianchi, S D; Roccuzzo, M; Albrito, F; Ragona, R; Anglesio, S

    1996-01-01

    The growing use of dento-maxillo-facial radiographic examinations has been accompanied by the publication of a large number of studies on dosimetry. A thorough review of the literature is presented in this article. Most studies were carried out on tissue equivalent skull phantoms, while only a few were in vivo. The aim of the present study was to evaluate in vivo absorbed doses during Orthopantomography (OPT). Full Mouth Periapical Examination (FMPE) and Intraoral Tube Panoramic Radiography (ITPR). Measurements were made on 30 patients, reproducing clinical conditions, in 46 anatomical sites, with 24 intra- and 22 extra-oral thermoluminiscent dosimeters (TLDS). The highest doses were measured, in orthopantomography, at the right mandibular angle (1899 mu Gy) in FMPE on the right naso-labial fold (5640 mu Gy and in ITPR on the palatal surface of the left second upper molar (1936 mu Gy). Intraoral doses ranged from 21 mu Gy, in orthopantomography, to 4494 mu Gy in FMPE. Standard errors ranged from 142% in ITPR to 5% in orthopantomography. The highest rate of standard errors was found in FMPE and ITPR. The data collected in this trial are in agreement with others in major literature reports. Disagreements are probably due to different exam acquisition and data collections. Such differences, presented comparison in several sites, justify lower doses in FMPE and ITPR. Advantages and disadvantages of in vivo dosimetry of the maxillary region are discussed, the former being a close resemblance to clinical conditions of examination and the latter the impossibility of collecting values in depth of tissues. Finally, both ITPR and FMPE required lower doses than expected, and can be therefore reconsidered relative to their radiation risk.

  12. Range management visual impacts

    Treesearch

    Bruce R. Brown; David Kissel

    1979-01-01

    Historical overgrazing of western public rangelands has resulted in the passage of the Public Rangeland Improvement Act of 1978. The main purpose of this Act is to improve unsatisfactory range conditions. A contributing factor to unfavorable range conditions is adverse visual impacts. These visual impacts can be identified in three categories of range management: range...

  13. Automated Gamma Knife dose planning

    NASA Astrophysics Data System (ADS)

    Leichtman, Gregg S.; Aita, Anthony L.; Goldman, H. W.

    1998-06-01

    The Gamma Knife (Elekta Instruments, Inc., Atlanta, GA), a neurosurgical, highly focused radiation delivery device, is used to eradicate deep-seated anomalous tissue within the human brain by delivering a lethal dose of radiation to target tissue. This dose is the accumulated result of delivering sequential `shots' of radiation to the target where each shot is approximately 3D Gaussian in shape. The size and intensity of each shot can be adjusted by varying the time of radiation exposure and by using one of four collimator sizes ranging from 4 - 18 mm. Current dose planning requires that the dose plan be developed manually to cover the target, and only the target, with a desired minimum radiation intensity using a minimum number of shots. This is a laborious and subjective process which typically leads to suboptimal conformal target coverage by the dose. We have used adaptive simulated annealing/quenching followed by Nelder-Mead simplex optimization to automate the selection and placement of Gaussian-based `shots' to form a simulated dose plane. In order to make the computation of the problem tractable, the algorithm, based upon contouring and polygon clipping, takes a 2 1/2-D approach to defining the cost function. Several experiments have been performed where the optimizers have been given the freedom to vary the number of shots and the weight, collimator size, and 3D location of each shot. To data best results have been obtained by forcing the optimizers to use a fixed number of unweighted shots with each optimizer set free to vary the 3D location and collimator size of each shot. Our preliminary results indicate that this technology will radically decrease planning time while significantly increasing accuracy of conformal target coverage and reproducibility over current manual methods.

  14. Range Reference Notebook

    DTIC Science & Technology

    2006-10-15

    rifle grenade (inert), tin can lid, 15” tent peg 3 Table FRD-7. Fort Ritchie Sector 3 Representative Examples of Non-MEC Clutter Description 1/2...Appendix B—Indirect Fire Range Examples SITES ( ADI ) Adak Naval Air Facility, AK, Mitt Lake Mortar Range (FRI) Fort Ritchie...example range. B- ADI -1 Indirect-Fire Range,: Adak, AK, Mitt Lake Mortar Range Impact Area Site-Specific References – Adak NAF Foster Wheeler

  15. A Long-Range Precision Ranging System

    NASA Technical Reports Server (NTRS)

    Easterling, Mahlon

    1961-01-01

    A technique is presented that may be used for precision real-time continuous range measuring at long ranges. The technique uses a carrier that is phase modulated by a pseudo-random binary sequence. The characteristics of the sequence that make it acquirable are discussed. The general form of a receiver capable of tracking the carrier is given and is shown to be a kind of phase-locked loop. A two-loop system capable of tracking a pseudo-random sequence and its clock is given. The combination of the receiver and the sequence tracking system form a ranging receiver. The power division necessary between the carrier and the sidebands is shown to be determined by the noise bandwidths of the two tracking systems. The bandwidths necessary for tracking space probes and Earth satellites are given and some experiments in radar-tracking Earth satellites are described. Based on these experiments, estimates are made of the useful range of such a system in tracking space probes.

  16. Dose finding when the target dose is on a plateau of a dose-response curve: comparison of fully sequential designs.

    PubMed

    Ivanova, Anastasia; Xiao, Changfu

    2013-01-01

    Consider the problem of estimating a dose with a certain response rate. Many multistage dose-finding designs for this problem were originally developed for oncology studies where the mean dose-response is strictly increasing in dose. In non-oncology phase II dose-finding studies, the dose-response curve often plateaus in the range of interest, and there are several doses with the mean response equal to the target. In this case, it is usually of interest to find the lowest of these doses because higher doses might have higher adverse event rates. It is often desirable to compare the response rate at the estimated target dose with a placebo and/or active control. We investigate which of the several known dose-finding methods developed for oncology phase I trials is the most suitable when the dose-response curve plateaus. Some of the designs tend to spread the allocation among the doses on the plateau. Others, such as the continual reassessment method and the t-statistic design, concentrate allocation at one of the doses with the t-statistic design selecting the lowest dose on the plateau more frequently.

  17. Synthesis of nonionic-anionic colloidal systems based on alkaline and ammonium β-nonylphenol polyethyleneoxy (n = 3-20) propionates/dodecylbenzenesulfonates with prospects for food hygiene

    PubMed Central

    2012-01-01

    Background The main objective of this work was to obtain a binary system of surface-active components (nonionic soap – alkaline and/or ammonium dodecylbenzenesulfonate) with potential competences in food hygiene, by accessing a scheme of classical reactions (cyanoethylation, total acid hydrolysis and stoichiometric neutralization with inorganic alkaline and/or organic ammonium bases) adapted to heterogeneously polyethoxylated nonylphenols (n = 3-20). In the processing system mentioned, dodecylbenzenesulfonic acid, initially the acid catalyst for the exhaustive hydrolysis of β-nonylphenolpolyethyleneoxy (n = 3-20) propionitriles, becomes together with the nonionic soap formed the second surface-active component of the binary system. Results In the reaction scheme adopted the influence of the main operating (duration, temperature, molar ratio of reagents) and structural parameters (degree of oligomerization of the polyoxyethylene chain) on the processing yields for the synthetic steps was followed. The favorable role of the polyoxyethylene chain size is remarked, through its specific conformation and its alkaline cations sequestration competences on the yields of cyanoethylation, but also the beneficial influence of phase-transfer catalysts in the total acid hydrolysis step. The chemical stability of dodecylbenzenesulfonic acid (DBSH) at the temperature and strongly acidic pH of the reaction environment is confirmed. The controlled change of the amount of DBSH in the final binary system will later confer it potential colloidal competences in food hygiene receipts. Conclusions The preliminary synthetic tests performed confirmed the prospect of obtaining a broad range of useful colloidal competences in various food hygiene scenarios. PMID:22958389

  18. Neutron dose equivalent meter

    DOEpatents

    Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony

    1996-01-01

    A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.

  19. Synthesis of BaTiO[subscript 3]-20wt%CoFe[subscript 2]O[subscript 4] Nanocomposites via Spark Plasma Sintering

    SciTech Connect

    Ghosh, Dipankar; Han, Hyuksu; Nino, Juan C.; Subhash, Ghatu; Jones, Jacob L.

    2012-10-23

    Barium titanate-20wt% cobalt ferrite (BaTiO{sub 3}-20wt%CoFe{sub 2}O{sub 4}) nanocomposites were sintered from nanocrystalline BaTiO{sub 3} and CoFe{sub 2}O{sub 4} powders using spark plasma sintering (SPS) and pressureless sintering (PS) techniques. Using SPS, dense polycrystalline composites were obtained at a sintering temperature as low as 860 C and a time of 5 min whereas PS required a higher sintering temperature (1150 C) and time (120 min) to obtain similarly dense composites. Microstructural analysis of the composites showed that both the techniques retained nanocrystalline grain sizes after sintering. High resolution X-ray diffraction measurements revealed that the BaTiO{sub 3}-20wt%CoFe{sub 2}O{sub 4} composites sintered by the SPS technique did not exhibit formation of any new phase(s) due to reaction between the BaTiO{sub 3} and CoFe{sub 2}O{sub 4} phases during sintering. However, the PS technique resulted in the formation of additional phases (other than the BaTiO{sub 3} and CoFe{sub 2}O{sub 4} phases) in the composites. While the composites synthesized by SPS were of superior phase-purity, evidence of Fe diffusion from the spinel to the perovskite phase was found from X-ray diffraction and permittivity measurements.

  20. Internal dose following a major nuclear war

    SciTech Connect

    Peterson, K.R.; Shapiro, C.S. )

    1992-01-01

    The PATHWAY model results were used, in conjunction with a hypothetical major nuclear attack on the U.S., to arrive at the ratio of internal to external dose for humans from early (48 h) fallout. Considered were the four nuclides (137Cs, 89Sr, 90Sr, 131I) that account for most of the reconstructed whole-body committed equivalent dose from internal radiation in people who lived downwind of the Nevada Test Site during atmospheric tests. Effects of climate perturbations (the 'nuclear winter' effect) on food crops were considered. These could increase internal dose estimates, depending on the severity of the climate perturbations. Internal and external doses to humans for 10 locations within the U.S. have been calculated, with varying local conditions and varying assumption about their shelters. The estimated 50-y internal dose commitment ranged from 0.0-0.17 Sv, the 48-h external dose from 0.15-4.6 Sv. The resultant ratios of internal to external committed dose received in the first months (until food transport was restored) varied from less than 0.01 to about 0.2. In all cases examined, the total dose from early fallout was found to be dominated by the external dose.

  1. Internal dose following a major nuclear war.

    PubMed

    Peterson, K R; Shapiro, C S

    1992-01-01

    The PATHWAY model results were used, in conjunction with a hypothetical major nuclear attack on the U.S., to arrive at the ratio of internal to external dose for humans from early (48 h) fallout. Considered were the four nuclides (137Cs, 89Sr, 90Sr, 131I) that account for most of the reconstructed whole-body committed equivalent dose from internal radiation in people who lived downwind of the Nevada Test Site during atmospheric tests. Effects of climate perturbations (the "nuclear winter" effect) on food crops were considered. These could increase internal dose estimates, depending on the severity of the climate perturbations. Internal and external doses to humans for 10 locations within the U.S. have been calculated, with varying local conditions and varying assumption about their shelters. The estimated 50-y internal dose commitment ranged from 0.0-0.17 Sv, the 48-h external dose from 0.15-4.6 Sv. The resultant ratios of internal to external committed dose received in the first months (until food transport was restored) varied from less than 0.01 to about 0.2. In all cases examined, the total dose from early fallout was found to be dominated by the external dose.

  2. Adaption By Low Dose Radiation Exposure

    PubMed Central

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to “as low as reasonably achievable” (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations. PMID:26672725

  3. Limited range of motion

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003173.htm Limited range of motion To use the sharing features on this page, please enable JavaScript. Limited range of motion is a term meaning that a joint or ...

  4. Television Tracker Range Equation

    NASA Astrophysics Data System (ADS)

    Huan-Wen, Zhu

    1987-05-01

    The paper gives an approximate television tracker range equation based on the concept of the radiology and signal-to-noise of television system, and describes the physical process and mathematical method of reckoning range equation. The range equation is useful to the desing and development of a system. This paper also discusses the demand and selection standard of the television tracker system to the imaging device and gives some possible approaches to increase the range.

  5. RADIO RANGING DEVICE

    DOEpatents

    Nieset, R.T.

    1961-05-16

    A radio ranging device is described. It utilizes a super regenerative detector-oscillator in which echoes of transmitted pulses are received in proper phase to reduce noise energy at a selected range and also at multiples of the selected range.

  6. Long Range Technology Planning.

    ERIC Educational Resources Information Center

    Ambron, Sueann, Ed.

    1986-01-01

    This summary of a meeting of the Apple Education Advisory Council, on long range technology plans at the state, county, district, and school levels, includes highlights from group discussions on future planning, staff development, and curriculum. Three long range technology plans at the state level are provided: Long Range Educational Technology…

  7. Long Range Technology Planning.

    ERIC Educational Resources Information Center

    Ambron, Sueann, Ed.

    1986-01-01

    This summary of a meeting of the Apple Education Advisory Council, on long range technology plans at the state, county, district, and school levels, includes highlights from group discussions on future planning, staff development, and curriculum. Three long range technology plans at the state level are provided: Long Range Educational Technology…

  8. Tau ranging revisited

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1987-01-01

    It is shown that a ranging receiver with a sufficient and reasonable number of correlators is competitive with the current sequential component ranging system by some 1.5 to 2.5 dB. The optimum transmitter code, the optimum receiver, and a near-maximum-lilelihood range-estimation algorithm are presented.

  9. A Meta-Analysis of Retention in Methadone Maintenance by Dose and Dosing Strategy

    PubMed Central

    Bao, Yan-ping; Liu, Zhi-min; Epstein, David H.; Du, Cun; Shi, Jie; Lu, Lin

    2013-01-01

    Objective To estimate, via meta-analysis, the influence of different methadone dose ranges and dosing strategies on retention rates in methadone maintenance treatment (MMT). Methods A systematic literature search identified 18 randomized controlled trials (RCTs) evaluating methadone dose and retention. Retention was defined as the percentage of patients remaining in treatment at a specified time point. After initial univariate analyses of retention by Pearson chi-squares, we used multilevel logistic regression to calculate summary odds ratios (ORs) and 95% confidence intervals for the effects of methadone dose (above or below 60 mg/day), flexible vs. fixed dosing strategy, and duration of follow-up. Results The total number of opioid-dependent participants in the 18 studies was 2831, with 1797 in MMT and 1034 receiving alternative mediations or placebo. Each variable significantly predicted retention with the other variables controlled for. Retention was greater with methadone doses ≥ 60 than with doses <60 (OR: 1.74, 95% CI: 1.43–2.11). Similarly, retention was greater with flexible-dose strategies than with fixed-dose strategies (OR: 1.72, 95% CI: 1.41–2.11). Conclusions Higher doses of methadone and individualization of doses are each independently associated with better retention in MMT. PMID:19152203

  10. Simulation of dose reduction in tomosynthesis

    SciTech Connect

    Svalkvist, Angelica; Baath, Magnus

    2010-01-15

    Purpose: Methods for simulating dose reduction are valuable tools in the work of optimizing radiographic examinations. Using such methods, clinical images can be simulated to have been collected at other, lower, dose levels without the need of additional patient exposure. A recent technology introduced to healthcare that needs optimization is tomosynthesis, where a number of low-dose projection images collected at different angles is used to reconstruct section images of an imaged object. The aim of the present work was to develop a method of simulating dose reduction for digital radiographic systems, suitable for tomosynthesis. Methods: The developed method uses information about the noise power spectrum (NPS) at the original dose level and the simulated dose level to create a noise image that is added to the original image to produce an image that has the same noise properties as an image actually collected at the simulated dose level. As the detective quantum efficiency (DQE) of digital detectors operating at the low dose levels used for tomosynthesis may show a strong dependency on the dose level, it is important that a method for simulating dose reduction for tomosynthesis takes this dependency into account. By applying an experimentally determined relationship between pixel mean and pixel variance, variations in both dose and DQE in relevant dose ranges are taken into account. Results: The developed method was tested on a chest tomosynthesis system and was shown to produce NPS of simulated dose-reduced projection images that agreed well with the NPS of images actually collected at the simulated dose level. The simulated dose reduction method was also applied to tomosynthesis examinations of an anthropomorphic chest phantom, and the obtained noise in the reconstructed section images was very similar to that of an examination actually performed at the simulated dose level. Conclusions: In conclusion, the present article describes a method for simulating dose

  11. Absorbed doses from temporomandibular joint radiography

    SciTech Connect

    Brooks, S.L.; Lanzetta, M.L.

    1985-06-01

    Thermoluminescent dosimeters were used in a tissue-equivalent phantom to measure doses of radiation absorbed by various structures in the head when the temporomandibular joint was examined by four different radiographic techniques--the transcranial, transorbital, and sigmoid notch (Parma) projections and the lateral tomograph. The highest doses of radiation occurred at the point of entry for the x-ray beam, ranging from 112 mrad for the transorbital view to 990 mrad for the sigmoid notch view. Only the transorbital projection a radiation dose to the lens of the eye. Of the four techniques evaluated, the lateral tomograph produced the highest doses to the pituitary gland and the bone marrow, while the sigmoid notch radiograph produced the highest doses to the parotid gland.

  12. Factors for converting dose measured in polystyrene phantoms to dose reported in water phantoms for incident proton beams.

    PubMed

    Moyers, M F; Vatnitsky, A S; Vatnitsky, S M

    2011-10-01

    Previous dosimetry protocols allowed calibrations of proton beamline dose monitors to be performed in plastic phantoms. Nevertheless, dose determinations were referenced to absorbed dose-to-muscle or absorbed dose-to-water. The IAEA Code of Practice TRS 398 recommended that dose calibrations be performed with ionization chambers only in water phantoms because plastic-to-water dose conversion factors were not available with sufficient accuracy at the time of its writing. These factors are necessary, however, to evaluate the difference in doses delivered to patients if switching from calibration in plastic to a protocol that only allows calibration in water. This work measured polystyrene-to-water dose conversion factors for this purpose. Uncertainties in the results due to temperature, geometry, and chamber effects were minimized by using special experimental set-up procedures. The measurements were validated by Monte Carlo simulations. At the peak of non-range-modulated beams, measured polystyrene-to-water factors ranged from 1.015 to 1.024 for beams with ranges from 36 to 315 mm. For beams with the same ranges and medium sized modulations, the factors ranged from 1.005 to 1.019. The measured results were used to generate tables of polystyrene-to-water dose conversion factors. The dose conversion factors can be used at clinical proton facilities to support beamline and patient specific dose per monitor unit calibrations performed in polystyrene phantoms.

  13. Factors for converting dose measured in polystyrene phantoms to dose reported in water phantoms for incident proton beams

    SciTech Connect

    Moyers, M. F.; Vatnitsky, A. S.; Vatnitsky, S. M.

    2011-10-15

    Purpose: Previous dosimetry protocols allowed calibrations of proton beamline dose monitors to be performed in plastic phantoms. Nevertheless, dose determinations were referenced to absorbed dose-to-muscle or absorbed dose-to-water. The IAEA Code of Practice TRS 398 recommended that dose calibrations be performed with ionization chambers only in water phantoms because plastic-to-water dose conversion factors were not available with sufficient accuracy at the time of its writing. These factors are necessary, however, to evaluate the difference in doses delivered to patients if switching from calibration in plastic to a protocol that only allows calibration in water. Methods: This work measured polystyrene-to-water dose conversion factors for this purpose. Uncertainties in the results due to temperature, geometry, and chamber effects were minimized by using special experimental set-up procedures. The measurements were validated by Monte Carlo simulations. Results: At the peak of non-range-modulated beams, measured polystyrene-to-water factors ranged from 1.015 to 1.024 for beams with ranges from 36 to 315 mm. For beams with the same ranges and medium sized modulations, the factors ranged from 1.005 to 1.019. The measured results were used to generate tables of polystyrene-to-water dose conversion factors. Conclusions: The dose conversion factors can be used at clinical proton facilities to support beamline and patient specific dose per monitor unit calibrations performed in polystyrene phantoms.

  14. Telemetry Ranging: Signal Processing

    NASA Astrophysics Data System (ADS)

    Hamkins, J.; Kinman, P.; Xie, H.; Vilnrotter, V.; Dolinar, S.

    2016-02-01

    This article describes the details of the signal processing used in a telemetry ranging system in which timing information is extracted from the downlink telemetry signal in order to compute spacecraft range. A previous article describes telemetry ranging concepts and architecture, which are a slight variation of a scheme published earlier. As in that earlier work, the telemetry ranging concept eliminates the need for a dedicated downlink ranging signal to communicate the necessary timing information. The present article describes the operation and performance of the major receiver functions on the spacecraft and the ground --- many of which are standard tracking loops already in use in JPL's flight and ground radios --- and how they can be used to provide the relevant information for making a range measurement. It also describes the implementation of these functions in software, and performance of an end-to-end software simulation of the telemetry ranging system.

  15. Sesame allergy threshold dose distribution.

    PubMed

    Dano, D; Remington, B C; Astier, C; Baumert, J L; Kruizinga, A G; Bihain, B E; Taylor, S L; Kanny, G

    2015-09-01

    Sesame is a relevant food allergen in France. Compared to other allergens there is a lack of food challenge data and more data could help sesame allergy risk management. The aim of this study is to collect more sesame challenge data and investigate the most efficient food challenge method for future studies. Records of patients at University Hospital in Nancy (France) with objective symptoms to sesame challenges were collected and combined with previously published data. An estimation of the sesame allergy population threshold was calculated based on individual NOAELs and LOAELs. Clinical dosing schemes at Nancy were investigated to see if the optimal protocol for sesame is currently used. Fourteen patients (10 M/4 F, 22 ± 14.85 years old) with objective symptoms were added to previously published data making a total of 35 sesame allergic patients. The most sensitive patient reacted to the first dose at challenge of 1.02 mg sesame protein. The ED05 ranges between 1.2 and 4.0 mg of sesame protein (Log-Normal, Log-Logistic, and Weibull models) and the ED10 between 4.2 and 6.2 mg. The optimal food challenge dosing scheme for sesame follows semi-log dose increases from 0.3 to 3000 mg protein. This article provides a valuable update to the existing clinical literature regarding sesame NOAELs and LOAELs. Establishment of a population threshold for sesame could help in increasing the credibility of precautionary labelling and decrease the costs associated with unexpected allergic reactions. Also, the use of an optimal dosing scheme would decrease time spent on diagnostic and thereafter on the economic burden of sesame allergy diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Telemetry-Based Ranging

    NASA Technical Reports Server (NTRS)

    Hamkins, Jon; Vilnrotter, Victor A.; Andrews, Kenneth S.; Shambayati, Shervin

    2011-01-01

    A telemetry-based ranging scheme was developed in which the downlink ranging signal is eliminated, and the range is computed directly from the downlink telemetry signal. This is the first Deep Space Network (DSN) ranging technology that does not require the spacecraft to transmit a separate ranging signal. By contrast, the evolutionary ranging techniques used over the years by NASA missions, including sequential ranging (transmission of a sequence of sinusoids) and PN-ranging (transmission of a pseudo-noise sequence) whether regenerative (spacecraft acquires, then regenerates and retransmits a noise-free ranging signal) or transparent (spacecraft feeds the noisy demodulated uplink ranging signal into the downlink phase modulator) relied on spacecraft power and bandwidth to transmit an explicit ranging signal. The state of the art in ranging is described in an emerging CCSDS (Consultative Committee for Space Data Systems) standard, in which a pseudo-noise (PN) sequence is transmitted from the ground to the spacecraft, acquired onboard, and the PN sequence is coherently retransmitted back to the ground, where a delay measurement is made between the uplink and downlink signals. In this work, the telemetry signal is aligned with the uplink PN code epoch. The ground station computes the delay between the uplink signal transmission and the received downlink telemetry. Such a computation is feasible because symbol synchronizability is already an integral part of the telemetry design. Under existing technology, the telemetry signal cannot be used for ranging because its arrival-time information is not coherent with any Earth reference signal. By introducing this coherence, and performing joint telemetry detection and arrival-time estimation on the ground, a high-rate telemetry signal can provide all the precision necessary for spacecraft ranging.

  17. MDSC, electrical conductivity and optical absorption studies of 40B 2O 3-20CdO-(40-x)Bi 2O 3-xLi 2O glasses

    NASA Astrophysics Data System (ADS)

    Vijaya Kumar, R.; Srinivasu, Ch.; Siva Kumar, K.

    2011-02-01

    Quaternary glasses with composition 40B 2O 3-20CdO-(40-x)Bi 2O 3-xLi 2O where 0 ≤ x ≤ 40 were prepared by melt quench technique. The density of the glass samples which is evaluated by Archimedes method showed that the density increases with Bi 2O 3 content. The modulated differential scanning calorimetry (MDSC) studies have been done on these samples to evaluate various thermo dynamical parameters. The value of glass transition temperature (T g) decreases with the Li 2O content. The dc electrical conductivity studies revealed that the conductivity in these glass samples increases with Li 2O content, where as the activation energy decreases. Theoretical optical basicity values decreases with Li 2O content. The optical absorption studies revealed that the cutoff wavelength increases while optical band gap energy (E opt) and Urbach energy (Δ E) decreases with increase of Li 2O content. The E opt values of these glasses are found to be in the range 2.848-3.258 eV where as the values of Δ E lies in the range 0.21-0.33 eV.

  18. A dose-ranging study of MF59®-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination

    PubMed Central

    Reisinger, Keith S; Holmes, Sandra J; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria

    2014-01-01

    Background During development of an A/H1N1 pandemic influenza vaccine, this study was performed to identify the antigen and adjuvant content which would provide optimal antibody response and persistence in adults and the elderly. Dose-sparing strategies, such as inclusion of adjuvants, are critical in ensuring the widest possible population coverage in the event of an influenza pandemic, despite a limited global capacity for vaccine manufacture. Methods Healthy subjects aged 18−64 years (n = 1240) and ≥65 years (n = 1352) were vaccinated with 1 of 8 investigational vaccine formulations varying in antigen quantity (3.75 µg to 30 µg of hemagglutinin) and MF59® adjuvant (none, half dose, or full dose). All subjects received 2 vaccine doses administered 3 weeks apart. Antibody response was assessed by hemagglutination inhibition assay 1 and 3 weeks after administration of first and second doses. Antibody persistence was assessed after 6 and 12 mo. Vaccine safety was monitored over 12 mo. Results All 8 investigational A/H1N1 vaccine formulations were well tolerated, and rapidly induced high antibody titers which met all of the Center for Biologics Evaluation and Research (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria 3 weeks after one dose. The highest antibody titers were observed in participants vaccinated with higher quantities of antigen and adjuvant. Conclusion A single vaccine dose containing 3.75 µg of A/California/7/2009 (H1N1) antigen with MF59 adjuvant was identified as optimal for young to middle-aged (18−64 years) and older (≥65 years) adult populations. PMID:25424947

  19. Calculation of effective dose.

    PubMed

    McCollough, C H; Schueler, B A

    2000-05-01

    The concept of "effective dose" was introduced in 1975 to provide a mechanism for assessing the radiation detriment from partial body irradiations in terms of data derived from whole body irradiations. The effective dose is the mean absorbed dose from a uniform whole-body irradiation that results in the same total radiation detriment as from the nonuniform, partial-body irradiation in question. The effective dose is calculated as the weighted average of the mean absorbed dose to the various body organs and tissues, where the weighting factor is the radiation detriment for a given organ (from a whole-body irradiation) as a fraction of the total radiation detriment. In this review, effective dose equivalent and effective dose, as established by the International Commission on Radiological Protection in 1977 and 1990, respectively, are defined and various methods of calculating these quantities are presented for radionuclides, radiography, fluoroscopy, computed tomography and mammography. In order to calculate either quantity, it is first necessary to estimate the radiation dose to individual organs. One common method of determining organ doses is through Monte Carlo simulations of photon interactions within a simplified mathematical model of the human body. Several groups have performed these calculations and published their results in the form of data tables of organ dose per unit activity or exposure. These data tables are specified according to particular examination parameters, such as radiopharmaceutical, x-ray projection, x-ray beam energy spectra or patient size. Sources of these organ dose conversion coefficients are presented and differences between them are examined. The estimates of effective dose equivalent or effective dose calculated using these data, although not intended to describe the dose to an individual, can be used as a relative measure of stochastic radiation detriment. The calculated values, in units of sievert (or rem), indicate the amount of

  20. Red bone marrow doses, integral absorbed doses, and somatically effective dose equivalent from four maxillary occlusal projections

    SciTech Connect

    Berge, T.I.; Wohni, T.

    1984-02-01

    Phantom measurements of red bone marrow (RBM) doses, integral absorbed doses, and somatically effective dose equivalent (SEDE) from four different maxillary occlusal projections are presented. For each projection, different combinations of focus-skin distances and tube potentials were compared with regard to the patient's radiation load. The axial incisal view produced the highest patient exposures, with a maximum red bone marrow dose of 122.5 microGy/exposure, integral absorbed dose of 8.6 mJ/exposure, and SEDE values of 39.6 microSv/exposure. The corresponding values from the frontal, lateral occlusal, and tuber views ranged between 4% and 44% of the axial incisal view values for the integral absorbed dose and SEDE values, and between 0.3% and 3% for the red bone marrow doses. Increasing the focus-skin distance from 17.5 cm to 27 cm is accompanied by a 24% to 30% reduction in integral absorbed dose. Increasing the tube potential from 50 kV to 65 kV likewise results in a 23% reduction in absorbed energy.

  1. Micron Accurate Absolute Ranging System: Range Extension

    NASA Technical Reports Server (NTRS)

    Smalley, Larry L.; Smith, Kely L.

    1999-01-01

    The purpose of this research is to investigate Fresnel diffraction as a means of obtaining absolute distance measurements with micron or greater accuracy. It is believed that such a system would prove useful to the Next Generation Space Telescope (NGST) as a non-intrusive, non-contact measuring system for use with secondary concentrator station-keeping systems. The present research attempts to validate past experiments and develop ways to apply the phenomena of Fresnel diffraction to micron accurate measurement. This report discusses past research on the phenomena, and the basis of the use Fresnel diffraction distance metrology. The apparatus used in the recent investigations, experimental procedures used, preliminary results are discussed in detail. Continued research and equipment requirements on the extension of the effective range of the Fresnel diffraction systems is also described.

  2. Structural studies of xLi2O-(40 - x)Bi2O3-20CdO-40B2O3 glasses

    NASA Astrophysics Data System (ADS)

    Vijaya Kumar, R.; Gayathri Pavani, P.; Ramesh, B.; Shareefuddin, Md.; Siva Kumar, K.

    2013-10-01

    Raman and infrared spectroscopies have been employed to investigate the xLi2O-(40 - x)Bi2O3-20CdO-40B2O3 glasses in order to obtain information about the competitive role of Bi2O3 and B2O3 in the formation of glass network. IR and Raman spectra show that these glasses are made up of [BO3], [BO4] and [BiO3] pyramidal and [BiO6] octahedral units. The formation of CdO4 in tetrahedral co-ordination was not observed. The optical absorption studies revealed that the cut-off wavelength decreases while optical band gap energy (Eopt) increases. The average electronic polarizability of the oxide ion (α), optical basicity Λ(Eopt), and Yamashita-Kurosawa's interaction parameter A(Eopt) were also examined.

  3. Compressive laser ranging.

    PubMed

    Babbitt, Wm Randall; Barber, Zeb W; Renner, Christoffer

    2011-12-15

    Compressive sampling has been previously proposed as a technique for sampling radar returns and determining sparse range profiles with a reduced number of measurements compared to conventional techniques. By employing modulation on both transmission and reception, compressive sensing in ranging is extended to the direct measurement of range profiles without intermediate measurement of the return waveform. This compressive ranging approach enables the use of pseudorandom binary transmit waveforms and return modulation, along with low-bandwidth optical detectors to yield high-resolution ranging information. A proof-of-concept experiment is presented. With currently available compact, off-the-shelf electronics and photonics, such as high data rate binary pattern generators and high-bandwidth digital optical modulators, compressive laser ranging can readily achieve subcentimeter resolution in a compact, lightweight package.

  4. Laser Ranging System

    NASA Technical Reports Server (NTRS)

    Russell, J. K.

    1986-01-01

    Laser system points and focuses TV camera. Ranger is modified stock distance-measuring unit mounted on and electrically connected to television camera. Effective over target range of 3 to 500 ft. (approximately 1 to 150m). Developed for television monitoring of nearby objects from Space Shuttle. Super-imposes range and range-rate (speed of approach or recession) data on television image of target. Principle adaptable to applications such as proximity warning and robot control.

  5. Improved ranging systems

    NASA Technical Reports Server (NTRS)

    Young, Larry E.

    1989-01-01

    Spacecraft range measurements have provided the most accurate tests, to date, of some relativistic gravitational parameters, even though the measurements were made with ranging systems having error budgets of about 10 meters. Technology is now available to allow an improvement of two orders of magnitude in the accuracy of spacecraft ranging. The largest gains in accuracy result from the replacement of unstable analog components with high speed digital circuits having precisely known delays and phase shifts.

  6. SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

    SciTech Connect

    Park, J; Park, H; Lee, J; Kang, S; Lee, M; Suh, T; Lee, B

    2014-06-01

    Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from the whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea

  7. Automatic range selector

    DOEpatents

    McNeilly, Clyde E.

    1977-01-04

    A device is provided for automatically selecting from a plurality of ranges of a scale of values to which a meter may be made responsive, that range which encompasses the value of an unknown parameter. A meter relay indicates whether the unknown is of greater or lesser value than the range to which the meter is then responsive. The rotatable part of a stepping relay is rotated in one direction or the other in response to the indication from the meter relay. Various positions of the rotatable part are associated with particular scales. Switching means are sensitive to the position of the rotatable part to couple the associated range to the meter.

  8. Range criterion for separability

    SciTech Connect

    Ha, Kil-Chan

    2010-12-15

    Horodecki formulated a remarkable criterion for separability, which is called the range criterion. This range criterion was mostly used to show that some states with positive partial transpose are entangled. In this Brief Report, we show that the range criterion is also useful to find a convex combination of product states for a separable state. For this purpose, we give an example of density matrix, which is separable in a 2 x 3 system and entangled in a 3 x 2 system at the same time. Then we illustrate the usefulness of the range criterion with this example.

  9. Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

    PubMed

    Nielsen, Suzanne; Gisev, Natasa; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Larance, Briony; Campbell, Gabrielle; Shanahan, Marian; Blyth, Fiona; Lintzeris, Nicholas; Pearson, Sallie; Mattick, Richard; Degenhardt, Louisa

    2017-05-01

    To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. Descriptive, cross-sectional study, utilising a 7-day medication diary. Community-based treatment settings, Australia. A sample of 1101 people prescribed opioids for chronic non-cancer pain. Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Meeting The Joint Commission's Dose Incident Identification and External Benchmarking Requirements Using the ACR's Dose Index Registry.

    PubMed

    Bohl, Michael A; Goswami, Roopa; Strassner, Brett; Stanger, Paula

    2016-08-01

    The purpose of this investigation was to evaluate the potential of using the ACR's Dose Index Registry(®) to meet The Joint Commission's requirements to identify incidents in which the radiation dose index from diagnostic CT examinations exceeded the protocol's expected dose index range. In total, 10,970 records in the Dose Index Registry were statistically analyzed to establish both an upper and lower expected dose index for each protocol. All 2015 studies to date were then retrospectively reviewed to identify examinations whose total examination dose index exceeded the protocol's defined upper threshold. Each dose incident was then logged and reviewed per the new Joint Commission requirements. Facilities may leverage their participation in the ACR's Dose Index Registry to fully meet The Joint Commission's dose incident identification review and external benchmarking requirements. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  11. Radiation dose levels in pediatric chest CT: experience in 499 children evaluated with dual-source single-energy CT.

    PubMed

    Martine, Remy-Jardin; Santangelo, Teresa; Colas, Lucie; Jean-Baptiste, Faivre; Duhamel, Alain; Deschildre, Antoine; Remy, Jacques

    2017-02-01

    The availability of dual-source technology has introduced the possibility of scanning children at lower kVp with a high-pitch mode, combining high-speed data acquisition and high temporal resolution. To establish the radiation dose levels of dual-source, single-energy chest CT examinations in children. We retrospectively recorded the dose-length product (DLP) of 499 consecutive examinations obtained in children <50 kg, divided into five weight groups: group 1 (<10 kg, n = 129); group 2 (10-20 kg, n = 176); group 3 (20-30 kg, n = 99), group 4 (30-40 kg, n = 58) and group 5 (40-49 kg, n = 37). All CT examinations were performed with high temporal resolution (75 ms), a high-pitch mode and a weight-adapted selection of the milliamperage. CT examinations were obtained at 80 kVp with a milliamperage ranging between 40 mAs and 90 mAs, and a pitch of 2.0 (n = 162; 32.5%) or 3.0 (n = 337; 67.5%). The mean duration of data acquisition was 522.8 ± 192.0 ms (interquartile range 390 to 610; median 490). In the study population, the mean CT dose index volume (CTDIvol32) was 0.83 mGy (standard deviation [SD] 0.20 mGy; interquartile range 0.72 to 0.94; median 0.78); the mean DLP32 was 21.4 mGy.cm (SD 9.1 mGy.cm; interquartile range 15 to 25; median 19.0); and the mean size-specific dose estimate (SSDE) was 1.7 mGy (SD 0.4 mGy; interquartile range 1.5 to 1.9; median 1.7). The DLP32, CTDIvol32 and SSDE were found to be statistically significant in the five weight categories (P < 0.0001). This study establishes the radiation dose levels for dual-source, single-kVp chest CT from a single center. In the five weight categories, the median values varied 15-37 mGy.cm for the DLP32, 0.78-1.25 mGy for the CTDIvol32 and 1.6-2.1 mGy for the SSDE.

  12. Agriculture, Forestry, Range Resources

    NASA Technical Reports Server (NTRS)

    Crea, W. J., Jr.

    1973-01-01

    Significant results obtained from ERTS-1 observations of agriculture, forestry, and range resources are summarized. Four major parts are covered: (1) crop classification and mensuration; (2) timber and range resources survey and classification; (3) soil survey and mapping; and (4) subdiscipline areas.

  13. Laser ranging data analysis

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Near real-time Lageos laser ranging data are analyzed in terms of range bias, time bias, and internal precision, and estimates for earth orientation parameters X(sub p), Y(sub p), and UT1 are obtained. The results of these analyses are reported in a variety of formats. Copies of monthly summaries from November, 1986 through November, 1987 are included.

  14. Long Range Facilities Planning

    DTIC Science & Technology

    1982-04-01

    Richard Muther range facilities Many alterna- analysis indi- cated that if NASSCO ever expected to surpass its output of the last several years, current...Marine Engineers (SNAME) SP-1 Panel Meeting. The Maritime Administration had Richard Muther (an authority on long range facility planning) address a

  15. Home range and travels

    USGS Publications Warehouse

    Stickel, L.F.; King, John A.

    1968-01-01

    The concept of home range was expressed by Seton (1909) in the term 'home region,' which Burr (1940, 1943) clarified with a definition of home range and exemplified in a definitive study of Peromyscus in the field. Burt pointed out the ever-changing characteristics of home-range area and the consequent absence of boundaries in the usual sense--a finding verified by investigators thereafter. In the studies summarized in this paper, sizes of home ranges of Peromyscus varied within two magnitudes, approximately from 0.1 acre to ten acres, in 34 studies conducted in a variety of habitats from the seaside dunes of Florida to the Alaskan forests. Variation in sizes of home ranges was correlated with both environmental and physiological factors; with habitat it was conspicuous, both in the same and different regions. Food supply also was related to size of home range, both seasonally and in relation to habitat. Home ranges generally were smallest in winter and largest in spring, at the onset of the breeding season. Activity and size also were affected by changes in weather. Activity was least when temperatures were low and nights were bright. Effects of rainfall were variable. Sizes varied according to sex and age; young mice remained in the parents' range until they approached maturity, when they began to travel more widely. Adult males commonly had larger home ranges than females, although there were a number of exceptions. An inverse relationship between population density and size of home range was shown in several studies and probably is the usual relationship. A basic need for activity and exploration also appeared to influence size of home range. Behavior within the home range was discussed in terms of travel patterns, travels in relation to home sites and refuges, territory, and stability of size of home range. Travels within the home range consisted of repeated use of well-worn trails to sites of food, shelter, and refuge, plus more random exploratory travels

  16. Dosing of antibiotics in obesity.

    PubMed

    Janson, Brett; Thursky, Karin

    2012-12-01

    Obesity is becoming a major burden on healthcare systems worldwide. The management of infections is problematic due to both an increased risk of morbidity and mortality, as well as a lack of information about dosing of antibiotics in the obese population. Recommendations in this patient group are severely lacking, so clinicians need to consider pharmacokinetic/pharmacodynamic parameters and the relative risks of overdosing and underdosing. Since 2011, articles on a number of antibiotics have been published, including cefazolin/cephazolin, cefepime, cefoxitin, clindamycin, cotrimoxazole, daptomycin, ertapenem, levofloxacin, linezolid, meropenem, moxifloxacin, piperacillin/tazobactam and vancomycin. Obesity causes a number of changes, including an increase in volume of distribution and changes in hepatic metabolism and renal excretion. Several antibiotics have sufficient data to be able to make recommendations, whereas other antibiotics may need to make use of doses at the upper end of the recommended range, or utilize other dose modifications based on pharmacokinetic/pharmacodynamic parameters, in an attempt to reach adequate levels and achieve similar efficacy.

  17. Acetaminophen dosing for children

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000783.htm Acetaminophen dosing for children To use the sharing features ... much of this medicine can be harmful. How Acetaminophen Can Help Your Child Acetaminophen is used to ...

  18. Once daily dose gentamicin in neonates - is our dosing correct?

    PubMed

    Serane, Tiroumourougane V; Zengeya, Stanley; Penford, Gemma; Cooke, Jane; Khanna, Gitika; McGregor-Colman, Elle

    2009-07-01

    The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates >or=32 weeks of gestation and or=32 weeks of gestation and dose. In neonates with gestational age between 32 and 36 weeks, 14 out of 65 (22%) had trough serum concentration >2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty-eight babies had audiometric evaluation which was normal. A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two-fifths of neonates between 32 and 36 +/- 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32-36 weeks' neonates.

  19. Electron beam dose calculations.

    PubMed

    Hogstrom, K R; Mills, M D; Almond, P R

    1981-05-01

    Electron beam dose distributions in the presence of inhomogeneous tissue are calculated by an algorithm that sums the dose distribution of individual pencil beams. The off-axis dependence of the pencil beam dose distribution is described by the Fermi-Eyges theory of thick-target multiple Coulomb scattering. Measured square-field depth-dose data serve as input for the calculations. Air gap corrections are incorporated and use data from'in-air' measurements in the penumbra of the beam. The effective depth, used to evaluate depth-dose, and the sigma of the off-axis Gaussian spread against depth are calculated by recursion relations from a CT data matrix for the material underlying individual pencil beams. The correlation of CT number with relative linear stopping power and relative linear scattering power for various tissues is shown. The results of calculations are verified by comparison with measurements in a 17 MeV electron beam from the Therac 20 linear accelerator. Calculated isodose lines agree nominally to within 2 mm of measurements in a water phantom. Similar agreement is observed in cork slabs simulating lung. Calculations beneath a bone substitute illustrate a weakness in the calculation. Finally a case of carcinoma in the maxillary antrum is studied. The theory suggests an alternative method for the calculation of depth-dose of rectangular fields.

  20. Range Safety Systems

    NASA Technical Reports Server (NTRS)

    Schrock, Kenneth W.; Humphries, Ricky H. (Technical Monitor)

    2002-01-01

    The high kinetic and potential energy of a launch vehicle mandates there be a mechanism to minimize possible damage to provide adequate safety for the launch facilities, range, and, most importantly, the general public. The Range Safety System, sometimes called the Flight Termination System or Flight Safety System, provides the required level of safety. The Range Safety System section of the Avionics chapter will attempt to describe how adequate safety is provided, the system's design, operation, and it's interface with the rest of the launch vehicle.

  1. A CONCEPTUAL FRAMEWORK FOR MANAGING RADIATION DOSE TO PATIENTS IN DIAGNOSTIC RADIOLOGY USING REFERENCE DOSE LEVELS.

    PubMed

    Almén, Anja; Båth, Magnus

    2016-06-01

    The overall aim of the present work was to develop a conceptual framework for managing radiation dose in diagnostic radiology with the intention to support optimisation. An optimisation process was first derived. The framework for managing radiation dose, based on the derived optimisation process, was then outlined. The outset of the optimisation process is four stages: providing equipment, establishing methodology, performing examinations and ensuring quality. The optimisation process comprises a series of activities and actions at these stages. The current system of diagnostic reference levels is an activity in the last stage, ensuring quality. The system becomes a reactive activity only to a certain extent engaging the core activity in the radiology department, performing examinations. Three reference dose levels-possible, expected and established-were assigned to the three stages in the optimisation process, excluding ensuring quality. A reasonably achievable dose range is also derived, indicating an acceptable deviation from the established dose level. A reasonable radiation dose for a single patient is within this range. The suggested framework for managing radiation dose should be regarded as one part of the optimisation process. The optimisation process constitutes a variety of complementary activities, where managing radiation dose is only one part. This emphasises the need to take a holistic approach integrating the optimisation process in different clinical activities.

  2. SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

    SciTech Connect

    Han, C; Schultheiss, T

    2015-06-15

    Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) were used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.

  3. Preliminary error budget for an optical ranging system: Range, range rate, and differenced range observables

    NASA Technical Reports Server (NTRS)

    Folkner, W. M.; Finger, M. H.

    1990-01-01

    Future missions to the outer solar system or human exploration of Mars may use telemetry systems based on optical rather than radio transmitters. Pulsed laser transmission can be used to deliver telemetry rates of about 100 kbits/sec with an efficiency of several bits for each detected photon. Navigational observables that can be derived from timing pulsed laser signals are discussed. Error budgets are presented based on nominal ground stations and spacecraft-transceiver designs. Assuming a pulsed optical uplink signal, two-way range accuracy may approach the few centimeter level imposed by the troposphere uncertainty. Angular information can be achieved from differenced one-way range using two ground stations with the accuracy limited by the length of the available baseline and by clock synchronization and troposphere errors. A method of synchronizing the ground station clocks using optical ranging measurements is presented. This could allow differenced range accuracy to reach the few centimeter troposphere limit.

  4. SNOWY RANGE WILDERNESS, WYOMING.

    USGS Publications Warehouse

    Houston, Robert S.; Bigsby, Philip R.

    1984-01-01

    A mineral survey of the Snowy Range Wilderness in Wyoming was undertaken and was followed up with more detailed geologic and geochemical surveys, culminating in diamond drilling of one hole in the Snowy Range Wilderness. No mineral deposits were identified in the Snowy Range Wilderness, but inasmuch as low-grade uranium and associated gold resources were identified in rocks similar to those of the northern Snowy Range Wilderness in an area about 5 mi northeast of the wilderness boundary, the authors conclude that the northern half of the wilderness has a probable-resource potential for uranium and gold. Closely spaced drilling would be required to completely evaluate this mineral potential. The geologic terrane precludes the occurrence of fossil fuels.

  5. Mu-2 ranging

    NASA Technical Reports Server (NTRS)

    Martin, W. L.; Zygielbaum, A. I.

    1977-01-01

    The Mu-II Dual-Channel Sequential Ranging System designed as a model for future Deep Space Network ranging equipment is described. A list of design objectives is followed by a theoretical explanation of the digital demodulation techniques first employed in this machine. Hardware and software implementation are discussed, together with the details relating to the construction of the device. Two appendixes are included relating to the programming and operation of this equipment to yield the maximum scientific data.

  6. Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients.

    PubMed

    Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

    2014-10-01

    To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. There were 47,181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Estimating parasite host range.

    PubMed

    Dallas, Tad; Huang, Shan; Nunn, Charles; Park, Andrew W; Drake, John M

    2017-08-30

    Estimating the number of host species that a parasite can infect (i.e. host range) provides key insights into the evolution of host specialism and is a central concept in disease ecology. Host range is rarely estimated in real systems, however, because variation in species relative abundance and the detection of rare species makes it challenging to confidently estimate host range. We applied a non-parametric richness indicator to estimate host range in simulated and empirical data, allowing us to assess the influence of sampling heterogeneity and data completeness. After validating our method on simulated data, we estimated parasite host range for a sparsely sampled global parasite occurrence database (Global Mammal Parasite Database) and a repeatedly sampled set of parasites of small mammals from New Mexico (Sevilleta Long Term Ecological Research Program). Estimation accuracy varied strongly with parasite taxonomy, number of parasite occurrence records, and the shape of host species-abundance distribution (i.e. the dominance and rareness of species in the host community). Our findings suggest that between 20% and 40% of parasite host ranges are currently unknown, highlighting a major gap in our understanding of parasite specificity, host-parasite network structure, and parasite burdens. © 2017 The Author(s).

  8. Dose distribution for dental cone beam CT and its implication for defining a dose index

    PubMed Central

    Pauwels, R; Theodorakou, C; Walker, A; Bosmans, H; Jacobs, R; Horner, K; Bogaerts, R

    2012-01-01

    Objectives To characterize the dose distribution for a range of cone beam CT (CBCT) units, investigating different field of view sizes, central and off-axis geometries, full or partial rotations of the X-ray tube and different clinically applied beam qualities. The implications of the dose distributions on the definition and practicality of a CBCT dose index were assessed. Methods Dose measurements on CBCT devices were performed by scanning cylindrical head-size water and polymethyl methacrylate phantoms, using thermoluminescent dosemeters, a small-volume ion chamber and radiochromic films. Results It was found that the dose distribution can be asymmetrical for dental CBCT exposures throughout a homogeneous phantom, owing to an asymmetrical positioning of the isocentre and/or partial rotation of the X-ray source. Furthermore, the scatter tail along the z-axis was found to have a distinct shape, generally resulting in a strong drop (90%) in absorbed dose outside the primary beam. Conclusions There is no optimal dose index available owing to the complicated exposure geometry of CBCT and the practical aspects of quality control measurements. Practical validation of different possible dose indices is needed, as well as the definition of conversion factors to patient dose. PMID:22752320

  9. Geometries, stabilities and fragmental channels of neutral and charged sulfur clusters: Sn(Q) (n = 3-20, Q = 0, ±1).

    PubMed

    Jin, Yuanyuan; Maroulis, George; Kuang, Xiaoyu; Ding, Liping; Lu, Cheng; Wang, Jingjing; Lv, Jian; Zhang, Chuanzhao; Ju, Meng

    2015-05-28

    We have performed unbiased searches for the global minimum structures of neutral and charged sulfur clusters Sn(Q) (n = 3-20, Q = 0, ±1) relying on the CALYPSO structure searching method combined with density functional theory geometric optimization. Very accurate ab initio calculations are used to determine relative stabilities and energy ranking among competing low-lying isomers of the neutral and charged sulfur clusters obtained from the structure search. The harmonic vibrational analysis is also undertaken to assure that the optimized geometries are the true minima. It is shown that the most equilibrium geometries of sulfur clusters are closed three-dimensional (3D) helical rings, which is in agreement with the experimental observations. The binding energies, second-order energy differences, and highest occupied-lowest unoccupied molecular orbital (HOMO-LUMO) gaps of the considered species are calculated and analyzed systematically. Additionally, the fragmentation channels are determined and the results indicate that the Sn(Q) → S2 + Sn-2(Q) channel is a route that the small clusters (n = 3-10) favor, while the larger species (n = 13-20) prefer the Sn(Q) → S8 + Sn-8(Q) channel.

  10. Enhancement of NK cell-mediated lysis of non-small lung cancer cells by nPKC activator, ingenol 3,20 dibenzoate.

    PubMed

    Gong, Chenyuan; Yao, Chao; Xu, Zihang; Ni, Zhongya; Zhu, Xiaowen; Wang, Lixin; Yan, Xuewei; Zhou, Wuxiong; Zhu, Shiguo

    2017-03-01

    The IFN-γ production is crucial for NK cell-mediated lysis of cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards natural products, limited information is out there about natural products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung cancer (NSCLC) cells. IDB also significantly enhanced the NK cell-mediated lysis of NSCLC cells. Furthermore, PKC inhibitor, sotrastaurin abrogated IDB-induced IFN-γ production, degranulation and cytotoxicity, but did not affect IFN-γ production by NK cells without IDB treatment and NSCLC cell stimulation. The IFN-γ neutralization reversed the IDB-induced enhancement of NK cell mediated killing. In conclusion, our study indicated that IDB enhanced NK cell-mediated lysis of NSCLC cells is dependent on specific PKC mediated IFN-γ production and degranulation. Thus, IDB may have a promising application in clinic for NK cell-based cancer immunotherapy.

  11. Assessment of rain fade mitigation techniques in the EHF band on a Syracuse 3 20/44-GHz low elevation link

    NASA Astrophysics Data System (ADS)

    de Montera, L.; Barthès, L.; Mallet, C.; Golé, P.; Marsault, T.

    2010-01-01

    An Earth-to-satellite propagation experiment in the EHF band has been carried out within the framework of the Syracuse 3 program, which is a new generation French military SATCOM system. The originality of this experiment resides in the link's frequencies (20 GHz downlink and 44 GHz uplink) and its low elevation angle (17°). The first part of the article presents a statistical analysis of attenuation data providing the long-term statistics, frequency scaling ratios and fade durations. These results are compared to standard ITU models. The second part of the article is dedicated to the short-term forecasting of rain fade, useful for the implementation of Fade Mitigation Techniques (FMT). Firstly, the downlink attenuation is predicted based on a non-linear ARIMA-GARCH model. The prediction result is then separated into several physical components (gases, clouds and rain) that are scaled to the uplink frequency using specific frequency scaling factors. The performance of the model is assessed based on Syracuse 3 20/44-GHz data collected during a period of 1 year.

  12. Individualised medicine: why we need Bayesian dosing.

    PubMed

    Donagher, Joni; Martin, Jennifer H; Barras, Michael A

    2017-05-01

    Individualised drug dosing has been shown to improve patient outcomes and reduce adverse drug events. One method of individualised medicine is the Bayesian approach, which uses prior information about how the population responds to therapy, to inform clinicians about how a specific individual is responding to their current therapy. This information is then used to make changes to the dose. Studies using a Bayesian approach to adjust drug dosing have shown that clinicians are able to achieve a therapeutic range quicker than standard practice. If concentration is related to a pharmacodynamic end-point, this means that the drug will be more effective, and the side-effects will be minimised. Unfortunately, the software options to assist with Bayesian dosing in Australia are limited. The aims of this article are to demystify the concepts of Bayesian dosing, set the context of the Bayesian approach using reference to other dosing strategies and discuss its benefits over current dosing methods for a number of drugs. The article is targeted to medical and pharmacy clinicians, and there is a practical clinical case to demonstrate how this method could be used in everyday clinical practice. © 2017 Royal Australasian College of Physicians.

  13. Fetal radiation dose in computed tomography.

    PubMed

    Kelaranta, Anna; Kaasalainen, Touko; Seuri, Raija; Toroi, Paula; Kortesniemi, Mika

    2015-07-01

    The connection between recorded volumetric CT dose index (CTDI vol) and determined mean fetal dose (Df) was examined from metal-oxide-semiconductor field-effect transistor dose measurements on an anthropomorphic female phantom in four stages of pregnancy in a 64-slice CT scanner. Automated tube current modulation kept the mean Df fairly constant through all pregnancy stages in trauma (4.4-4.9 mGy) and abdomino-pelvic (2.1-2.4 mGy) protocols. In pulmonary angiography protocol, the mean Df increased exponentially as the distance from the end of the scan range decreased (0.01-0.09 mGy). For trauma protocol, the relative mean Df as a function of gestational age were in the range 0.80-0.97 compared with the mean CTDI vol. For abdomino-pelvic protocol, the relative mean Df was 0.57-0.79 and for pulmonary angiography protocol, 0.01-0.05 compared with the mean CTDI vol, respectively. In conclusion, if the fetus is in the primary beam, the CTDI vol can be used as an upper estimate of the fetal dose. If the fetus is not in the primary beam, the fetal dose can be estimated by considering also the distance of the fetus from the scan range.

  14. Estimated radiation dose from timepieces containing tritium

    SciTech Connect

    McDowell-Boyer, L M

    1980-01-01

    Luminescent timepieces containing radioactive tritium, either in elemental form or incorporated into paint, are available to the general public. The purpose of this study was to estimate potential radiation dose commitments received by the public annually as a result of exposure to tritium which may escape from the timepieces during their distribution, use, repair, and disposal. Much uncertainty is associated with final dose estimates due to limitations of empirical data from which exposure parameters were derived. Maximum individual dose estimates were generally less than 3 ..mu..Sv/yr, but ranged up to 2 mSv under worst-case conditions postulated. Estimated annual collective (population) doses were less than 5 person/Sv per million timepieces distributed.

  15. Simplified Warfarin Dose-response Pharmacodynamic Models

    PubMed Central

    Kim, Seongho; Gaweda, Adam E.; Wu, Dongfeng; Li, Lang; Rai, Shesh N.; Brier, Michael E.

    2014-01-01

    Warfarin is a frequently used oral anticoagulant for long-term prevention and treatment of thromboembolic events. Due to its narrow therapeutic range and large inter-individual dose-response variability, it is highly desirable to personalize warfarin dosing. However, the complexity of the conventional kinetic-pharmacodynamic (K-PD) models hampers the development of the personalized dose management. To avert this challenge, we propose simplified PD models for warfarin dose-response relationship, which is motivated by ideas from control theory. The simplified models were further applied to longitudinal data of 37 patients undergoing anticoagulation treatment using the standard two-stage approach and then compared with the conventional K-PD models. Data analysis shows that all models have a similar predictive ability, but the simplified models are most parsimonious. PMID:25750489

  16. Utirik Atoll Dose Assessment

    SciTech Connect

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  17. Laser Ranging Simulation Program

    NASA Technical Reports Server (NTRS)

    Piazolla, Sabino; Hemmati, Hamid; Tratt, David

    2003-01-01

    Laser Ranging Simulation Program (LRSP) is a computer program that predicts selected aspects of the performances of a laser altimeter or other laser ranging or remote-sensing systems and is especially applicable to a laser-based system used to map terrain from a distance of several kilometers. Designed to run in a more recent version (5 or higher) of the MATLAB programming language, LRSP exploits the numerical and graphical capabilities of MATLAB. LRSP generates a graphical user interface that includes a pop-up menu that prompts the user for the input of data that determine the performance of a laser ranging system. Examples of input data include duration and energy of the laser pulse, the laser wavelength, the width of the laser beam, and several parameters that characterize the transmitting and receiving optics, the receiving electronic circuitry, and the optical properties of the atmosphere and the terrain. When the input data have been entered, LRSP computes the signal-to-noise ratio as a function of range, signal and noise currents, and ranging and pointing errors.

  18. Derivation of Human Lethal Doses

    DTIC Science & Technology

    2006-01-19

    extrapolate to human lethal doses. In this effort, Ekwall et al. (1998) collected data on human lethal doses in acute poisonings from handbooks on...emergency medicine, pharmacology, forensic medicine, and industrial chemical toxicology, in addition to a poison information center. The authors presented...lethal doses would be dose-response data in people. Estimates of doses from case reports of fatal poisonings provide information on what doses can be

  19. ATS-3 ranging support

    NASA Technical Reports Server (NTRS)

    Brisken, A. F.

    1977-01-01

    The purpose of this effort was to provide NASA-Goddard Space Flight Center with ATS-3 ranging data from ground stations of the VHF network and from an additional ground station installed at the NASA-Goddard Space Flight Center. Ranging measurements to the NASA transponder enabled calculation of the transponder's line-of-position. Installation of an S-band transponder at the same site and the conduct of ranging experiments to this transponder and others via ATS-6 provided a second line-of-position. The NASA S-band transponder was specifically designed for installation aboard spacecraft. Consequently, this program provided NASA an opportunity to compare two different techniques using geostationary satellites in the tracking low orbit satellites.

  20. VENUS Ranging Study

    DTIC Science & Technology

    2014-12-01

    the two dimensional PECan modelling presented in the next section. The seamount at 30 km range from RC to CN has a significant effect on propagation...Gabriola Island there is an apparent ‘ seamount ’ in the bathymetry profiles of CN and EN at a range of 30 km from RC, see Figure 3. The sediment in the...region of the ‘ seamount ’ corresponds to the rock, gravel, and gravel and rock shown in Figure 5 intersecting each track off Gabriola Island. The

  1. Western Aeronautical Test Range

    NASA Technical Reports Server (NTRS)

    Sakahara, Robert D.

    2008-01-01

    This viewgraph presentation reviews the work of the Western Aeronautical Test Range (WATR). NASA's Western Aeronautical Test Range is a network of facilities used to support aeronautical research, science missions, exploration system concepts, and space operations. The WATR resides at NASA's Dryden Flight Research Center located at Edwards Air Force Base, California. The WATR is a part of NASA's Corporate Management of Aeronautical Facilities and funded by the Strategic Capability Asset Program (SCAP). Maps show the general location of the WATR area that is used for aeronautical testing and evaluation. The products, services and facilities of WATR are discussed,

  2. Himalayan Mountain Range, India

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Snow is present the year round in most of the high Himalaya Mountain Range (33.0N, 76.5E). In this view taken at the onset of winter, the continuous snow line can be seen for hundreds of miles along the south face of the range in the Indian states of Punjab and Kashmir. The snow line is at about 12,000 ft. altitude but the deep Cenab River gorge is easily delineated as a break along the south edge of the snow covered mountains. '

  3. Satellite Laser Ranging operations

    NASA Technical Reports Server (NTRS)

    Pearlman, Michael R.

    1994-01-01

    Satellite Laser Ranging (SLR) is currently providing precision orbit determination for measurements of: 1) Ocean surface topography from satellite borne radar altimetry, 2) Spatial and temporal variations of the gravity field, 3) Earth and ocean tides, 4) Plate tectonic and regional deformation, 5) Post-glacial uplift and subsidence, 6) Variations in the Earth's center-of-mass, and 7) Variations in Earth rotation. SLR also supports specialized programs in time transfer and classical geodetic positioning, and will soon provide precision ranging to support experiments in relativity.

  4. Broad host range plasmids.

    PubMed

    Jain, Aayushi; Srivastava, Preeti

    2013-11-01

    Plasmids are and will remain important cloning vehicles for biotechnology. They have also been associated with the spread of a number of diseases and therefore are a subject of environmental concern. With the advent of sequencing technologies, the database of plasmids is increasing. It will be of immense importance to identify the various bacterial hosts in which the plasmid can replicate. The present review article describes the features that confer broad host range to the plasmids, the molecular basis of plasmid host range evolution, and applications in recombinant DNA technology and environment.

  5. Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

    PubMed

    Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

    2017-06-01

    Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After

  6. Dose Reduction Techniques

    SciTech Connect

    WAGGONER, L.O.

    2000-05-16

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.

  7. Dose Calculation Spreadsheet

    SciTech Connect

    Simpkins, Ali

    1997-06-10

    VENTSAR XL is an EXCEL Spreadsheet that can be used to calculate downwind doses as a result of a hypothetical atmospheric release. Both building effects and plume rise may be considered. VENTSAR XL will run using any version of Microsoft EXCEL version 4.0 or later. Macros (the programming language of EXCEL) was used to automate the calculations. The user enters a minimal amount of input and the code calculates the resulting concentrations and doses at various downwind distances as specified by the user.

  8. Agriculture, forest, and range

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The findings and recommendations of the panel for developing a satellite remote-sensing global information system in the next decade are reported. User requirements were identified in five categories: (1) cultivated crops, (2) land resources, (3)water resources, (4)forest management, and (5) range management. The benefits from the applications of satellite data are discussed.

  9. RADIO RANGING DEVICE

    DOEpatents

    Bogle, R.W.

    1960-11-22

    A description is given of a super-regenerative oscillator ranging device provided with radiating and receiving means and being capable of indicating the occurrence of that distance between itself and a reflecting object which so phases the received echo of energy of a preceding emitted oscillation that the intervals between oscillations become uniform.

  10. Institutional Long Range Planning.

    ERIC Educational Resources Information Center

    Caldwell Community Coll. and Technical Inst., Lenoir, NC.

    Long-range institutional planning has been in effect at Caldwell Community College and Technical Institute since 1973. The first step in the process was the identification of planning areas: administration, organization, educational programs, learning resources, student services, faculty, facilities, maintenance/operation, and finances. The major…

  11. Long Range Plan.

    ERIC Educational Resources Information Center

    Jefferson Coll., Hillsboro, MO.

    This document presents Jefferson College's "Long Range Plan," which is intended to provide the College's governing board, administration, and faculty and staff with a task-oriented blueprint for maximizing the delivery of higher education services to students and the community in a predictable, programmatic, and fiscally sound manner.…

  12. Himalayan Mountain Range

    NASA Image and Video Library

    1981-04-14

    STS001-12-350 (12-14 April 1981) --- India and China, the Ladokh and Zaskar Ranges of the Great Himalaya are clearly etched by snow and shadow. A detailed view shows the glaciation process over a wide area. Photo credit: NASA

  13. Agriculture, forestry, range resources

    NASA Technical Reports Server (NTRS)

    Crea, W. J.

    1974-01-01

    In the area of crop specie identification, it has been found that temporal data analysis, preliminary stratification, and unequal probability analysis were several of the factors that contributed to high identification accuracies. Single data set accuracies on fields of greater than 80,000 sq m (20 acres) are in the 70- to 90-percent range; however, with the use of temporal data, accuracies of 95 percent have been reported. Identification accuracy drops off significantly on areas of less than 80,000 sq m (20 acres) as does measurement accuracy. Forest stratification into coniferous and deciduous areas has been accomplished to a 90- to 95-percent accuracy level. Using multistage sampling techniques, the timber volume of a national forest district has been estimated to a confidence level and standard deviation acceptable to the Forest Service at a very favorable cost-benefit time ratio. Range specie/plant community vegetation mapping has been accomplished at various levels of success (69- to 90-percent accuracy). However, several investigators have obtained encouraging initial results in range biomass (forage production) estimation and range readiness predictions. Soil association map correction and soil association mapping in new area appear to have been proven feasible on large areas; however, testing in a complex soil area should be undertaken.

  14. Agriculture, forestry, range resources

    NASA Technical Reports Server (NTRS)

    Macdonald, R. B.

    1974-01-01

    The necessary elements to perform global inventories of agriculture, forestry, and range resources are being brought together through the use of satellites, sensors, computers, mathematics, and phenomenology. Results of ERTS-1 applications in these areas, as well as soil mapping, are described.

  15. Electric vehicles: Driving range

    NASA Astrophysics Data System (ADS)

    Kempton, Willett

    2016-09-01

    For uptake of electric vehicles to increase, consumers' driving-range needs must be fulfilled. Analysis of the driving patterns of personal vehicles in the US now shows that today's electric vehicles can meet all travel needs on almost 90% of days from a single overnight charge.

  16. Front Range Branch Officers

    NASA Astrophysics Data System (ADS)

    The Front Range Branch of AGU has installed officers for 1990: Ray Noble, National Center for Atmospheric Research, chair; Sherry Oaks, U.S. Geological Survey, chair-elect; Howard Garcia, NOAA, treasurer; Catharine Skokan, Colorado School of Mines, secretary. JoAnn Joselyn of NOAA is past chair. Members at large are Wallace Campbell, NOAA; William Neff, USGS; and Stephen Schneider, NCAR.

  17. Nonscanning confocal ranging system

    NASA Astrophysics Data System (ADS)

    Sun, P. C.; Arons, E.

    1995-03-01

    We demonstrate a nonscanning confocal ranging system based on spatially incoherent interferometry. Such a system has significant advantages over the conventional confocal imaging system and other interferometric systems. We develop the theory in terms of coherence cells and demonstrate the equivalence of our method to the conventional confocal methods. Experimental results are also provided.

  18. Fact Sheet: Range Complex

    NASA Technical Reports Server (NTRS)

    Cornelson, C.; Fretter, E.

    2004-01-01

    NASA Ames has a long tradition in leadership with the use of ballistic ranges and shock tubes for the purpose of studying the physics and phenomena associated with hypervelocity flight. Cutting-edge areas of research run the gamut from aerodynamics, to impact physics, to flow-field structure and chemistry. This legacy of testing began in the NACA era of the 1940's with the Supersonic Free Flight Tunnel, and evolved dramatically up through the late 1950s with the pioneering work in the Ames Hypersonic Ballistic Range. The tradition continued in the mid-60s with the commissioning of the three newest facilities: the Ames Vertical Gun Range (AVGR) in 1964, the Hypervelocity Free Flight Facility (HFFF) in 1965 and the Electric Arc Shock Tube (EAST) in 1966. Today the Range Complex continues to provide unique and critical testing in support of the Nation's programs for planetary geology and geophysics; exobiology; solar system origins; earth atmospheric entry, planetary entry, and aerobraking vehicles; and various configurations for supersonic and hypersonic aircraft.

  19. STDN ranging equipment

    NASA Technical Reports Server (NTRS)

    Jones, C. E.

    1975-01-01

    Final results of the Spaceflight Tracking and Data Network (STDN) Ranging Equipment program are summarized. Basic design concepts and final design approaches are described. Theoretical analyses which define requirements and support the design approaches are presented. Design verification criteria are delineated and verification test results are specified.

  20. Mobile satellite ranging

    NASA Technical Reports Server (NTRS)

    Silverberg, E. C.

    1978-01-01

    A brief review of the constraints which have limited satellite ranging hardware and an outline of the steps which are underway to improve the status of the equipment in this area are given. In addition, some suggestions are presented for the utilization of newer instruments and for possible future research and development work in this area.

  1. Eye lens dose in interventional cardiology.

    PubMed

    Principi, S; Delgado Soler, C; Ginjaume, M; Beltran Vilagrasa, M; Rovira Escutia, J J; Duch, M A

    2015-07-01

    The ICRP has recently recommended reducing the occupational exposure dose limit for the lens of the eye to 20 mSv y(-1), averaged over a period of 5 y, with no year exceeding 50 mSv, instead of the current 150 mSv y(-1). This reduction will have important implications for interventional cardiology and radiology (IC/IR) personnel. In this work, lens dose received by a staff working in IC is studied in order to determine whether eye lens dose monitoring or/and additional radiological protection measures are required. Eye lens dose exposure was monitored in 10 physicians and 6 nurses. The major IC procedures performed were coronary angiography and percutaneous transluminal coronary angioplasty. The personnel were provided with two thermoluminescent dosemeters (TLDs): one calibrated in terms of Hp(3) located close to the left ear of the operator and a whole-body dosemeter calibrated in terms of Hp(10) and Hp(0.07) positioned on the lead apron. The estimated annual eye lens dose for physicians ranged between 8 and 60 mSv, for a workload of 200 procedures y(-1). Lower doses were collected for nurses, with estimated annual Hp(3) between 2 and 4 mSv y(-1). It was observed that for nurses the Hp(0.07) measurement on the lead apron is a good estimate of eye lens dose. This is not the case for physicians, where the influence of both the position and use of protective devices such as the ceiling shield is very important and produces large differences among doses both at the eyes and on the thorax. For physicians, a good correlation between Hp(3) and dose area product is shown. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Space-Based Range

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Space-Based Range (SBR), previously known as Space-Based Telemetry and Range Safety (STARS), is a multicenter NASA proof-of-concept project to determine if space-based communications using NASA's Tracking and Data Relay Satellite System (TDRSS) can support the Range Safety functions of acquiring tracking data and generating flight termination signals, while also providing broadband Range User data such as voice, video, and vehicle/payload data. There was a successful test of the Range Safety system at Wallops Flight Facility (WFF) on December 20, 2005, on a two-stage Terrier-Orion spin-stabilized sounding rocket. SBR transmitted GPS tracking data and maintained links with two TDRSS satellites simultaneously during the 10-min flight. The payload section deployed a parachute, landed in the Atlantic Ocean about 90 miles downrange from the launch site, and was successfully recovered. During the Terrier-Orion tests flights, more than 99 percent of all forward commands and more than 95 percent of all return frames were successfully received and processed. The time latency necessary for a command to travel from WFF over landlines to White Sands Complex and then to the vehicle via TDRSS, be processed onboard, and then be sent back to WFF was between 1.0 s and 1.1 s. The forward-link margins for TDRS-10 (TDRS East [TDE]) were 11 dB to 12 dB plus or minus 2 dB, and for TDRS-4 (TDRS Spare [TDS]) were 9 dB to 10 dB plus or minus 1.5 dB. The return-link margins for both TDE and TDS were 6 dB to 8 dB plus or minus 3 dB. There were 11 flights on an F-15B at Dryden Flight Research Center (DFRC) between November 2006 and February 2007. The Range User system tested a 184-element TDRSS Ku-band (15 GHz) phased-array antenna with data rates of 5 Mbps and 10 Mbps. This data was a combination of black-and-white cockpit video, Range Safety tracking and transceiver data, and aircraft and antenna controller data streams. IP data formatting was used.

  3. Efficacy of Extended-Interval Dosing of Micafungin Evaluated Using a Pharmacokinetic/Pharmacodynamic Study with Humanized Doses in Mice

    PubMed Central

    Lepak, A.; Marchillo, K.; VanHecker, J.; Azie, N.

    2015-01-01

    The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of the echinocandins favor infrequent administration of large doses. The in vivo investigation reported here tested the utility of a range of humanized dose levels of micafungin using a variety of prolonged dosing intervals for the prevention and therapy of established disseminated candidiasis. Humanized doses of 600 mg administered every 6 days prevented fungal growth in prophylaxis. Humanized doses of 300 to 1,000 mg administered every 6 days demonstrated efficacy for established infections. PMID:26552968

  4. Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

    SciTech Connect

    Veres, Cristina; Allodji, Rodrigue S.; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Mège, Jean Pierre; Lefkopoulos, Dimitri; Quiniou, Eric; Deutsh, Eric; Vathaire, Florent de; Diallo, Ibrahima

    2014-12-01

    Purpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. Methods and Materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D{sub 50%}) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies.

  5. Doses metrics and patient age in CT.

    PubMed

    Huda, Walter; Tipnis, Sameer V

    2016-03-01

    The aim of this study was to investigate how effective dose and size-specific dose estimate (SSDE) change with patient age (size) for routine head and abdominal/pelvic CT examinations. Heads and abdomens of patients were modelled as a mass-equivalent cylinder of water corresponding to the patient 'effective diameter'. Head CT scans were performed at CTDIvol(S) of 40 mGy, and abdominal CT scans were performed at CTDIvol(L) of 10 mGy. Values of SSDE were obtained using conversion factors in AAPM Task Group Report 204. Age-specific scan lengths for head and abdominal CT scans obtained from the authors' clinical practice were used to estimate the dose-length product for each CT examination. Effective doses were calculated from previously published age- and sex-specific E/DLP conversion factors, based on ICRP 103 organ-weighting factors. For head CT examinations, the scan length increased from 15 cm in a newborn to 20 cm in adults, and for an abdominal/pelvic CT, the scan length increased from 20 cm in a newborn to 45 cm in adults. For head CT scans, SSDE ranged from 37.2 mGy in adults to 48.8 mGy in a newborn, an increase of 31 %. The corresponding head CT effective doses range from 1.4 mSv in adults to 5.2 mSv in a newborn, an increase of 270 %. For abdomen CT scans, SSDE ranged from 13.7 mGy in adults to 23.0 mGy in a newborn, an increase of 68 %. The corresponding abdominal CT effective doses ranged from 6.3 mSv in adults to 15.4 mSv in a newborn, an increase of 140 %. SSDE increases much less than effective dose in paediatric patients compared with adults because it does not account for scan length or scattered radiation. Size- and age-specific effective doses better quantify the total radiation received by patients in CT by explicitly accounting for all organ doses, as well as their relative radio sensitivity.

  6. Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

    SciTech Connect

    Holmes, W.G.

    2001-08-16

    The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

  7. In vivo proton range verification: a review

    NASA Astrophysics Data System (ADS)

    Knopf, Antje-Christin; Lomax, Antony

    2013-08-01

    Protons are an interesting modality for radiotherapy because of their well defined range and favourable depth dose characteristics. On the other hand, these same characteristics lead to added uncertainties in their delivery. This is particularly the case at the distal end of proton dose distributions, where the dose gradient can be extremely steep. In practice however, this gradient is rarely used to spare critical normal tissues due to such worries about its exact position in the patient. Reasons for this uncertainty are inaccuracies and non-uniqueness of the calibration from CT Hounsfield units to proton stopping powers, imaging artefacts (e.g. due to metal implants) and anatomical changes of the patient during treatment. In order to improve the precision of proton therapy therefore, it would be extremely desirable to verify proton range in vivo, either prior to, during, or after therapy. In this review, we describe and compare state-of-the art in vivo proton range verification methods currently being proposed, developed or clinically implemented.

  8. Automated size-specific CT dose monitoring program: Assessing variability in CT dose

    SciTech Connect

    Christianson, Olav; Li Xiang; Frush, Donald; Samei, Ehsan

    2012-11-15

    that were not adjusted by patient size. Additionally, considerable differences were noted in ED{sub adj} distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower ED{sub adj} (range: 9%-64%). Finally, a significant difference (up to 59%) in ED{sub adj} distributions was observed between institutions, indicating the potential for dose reduction. Conclusions: The authors developed a robust automated size-specific radiation dose monitoring program for CT. Using this program, significant differences in ED{sub adj} were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.

  9. When is a dose not a dose

    SciTech Connect

    Bond, V.P.

    1991-01-01

    Although an enormous amount of progress has been made in the fields of radiation protection and risk assessment, a number of significant problems remain. The one problem which transcends all the rest, and which has been subject to considerable misunderstanding, involves what has come to be known as the 'linear non-threshold hypothesis', or 'linear hypothesis'. Particularly troublesome has been the interpretation that any amount of radiation can cause an increase in the excess incidence of cancer. The linear hypothesis has dominated radiation protection philosophy for more than three decades, with enormous financial, societal and political impacts and has engendered an almost morbid fear of low-level exposure to ionizing radiation in large segments of the population. This document presents a different interpretation of the linear hypothesis. The basis for this view lies in the evolution of dose-response functions, particularly with respect to their use initially in the context of early acute effects, and then for the late effects, carcinogenesis and mutagenesis. 11 refs., 4 figs. (MHB)

  10. Range expansion of mutualists

    NASA Astrophysics Data System (ADS)

    Muller, Melanie J. I.; Korolev, Kirill S.; Murray, Andrew W.; Nelson, David R.

    2012-02-01

    The expansion of a species into new territory is often strongly influenced by the presence of other species. This effect is particularly striking for the case of mutualistic species that enhance each other's proliferation. Examples range from major events in evolutionary history, such as the spread and diversification of flowering plants due to their mutualism with pollen-dispersing insects, to modern examples like the surface colonisation of multi-species microbial biofilms. Here, we investigate the spread of cross-feeding strains of the budding yeast Saccharomyces cerevisiae on an agar surface as a model system for expanding mutualists. Depending on the degree of mutualism, the two strains form distinctive spatial patterns during their range expansion. This change in spatial patterns can be understood as a phase transition within a stepping stone model generalized to two mutualistic species.

  11. Long range chromatin organization

    PubMed Central

    Acuña, Luciana I Gómez; Kornblihtt, Alberto R

    2014-01-01

    Splicing is a predominantly co-transcriptional process that has been shown to be tightly coupled to transcription. Chromatin structure is a key factor that mediates this functional coupling. In light of recent evidence that shows the importance of higher order chromatin organization in the coordination and regulation of gene expression, we discuss here the possible roles of long-range chromatin organization in splicing and alternative splicing regulation. PMID:25764333

  12. Light beam range finder

    DOEpatents

    McEwan, Thomas E.

    1998-01-01

    A "laser tape measure" for measuring distance which includes a transmitter such as a laser diode which transmits a sequence of electromagnetic pulses in response to a transmit timing signal. A receiver samples reflections from objects within the field of the sequence of visible electromagnetic pulses with controlled timing, in response to a receive timing signal. The receiver generates a sample signal in response to the samples which indicates distance to the object causing the reflections. The timing circuit supplies the transmit timing signal to the transmitter and supplies the receive timing signal to the receiver. The receive timing signal causes the receiver to sample the reflection such that the time between transmission of pulses in the sequence in sampling by the receiver sweeps over a range of delays. The transmit timing signal causes the transmitter to transmit the sequence of electromagnetic pulses at a pulse repetition rate, and the received timing signal sweeps over the range of delays in a sweep cycle such that reflections are sampled at the pulse repetition rate and with different delays in the range of delays, such that the sample signal represents received reflections in equivalent time. The receiver according to one aspect of the invention includes an avalanche photodiode and a sampling gate coupled to the photodiode which is responsive to the received timing signal. The transmitter includes a laser diode which supplies a sequence of visible electromagnetic pulses. A bright spot projected on to the target clearly indicates the point that is being measured, and the user can read the range to that point with precision of better than 0.1%.

  13. Light beam range finder

    DOEpatents

    McEwan, T.E.

    1998-06-16

    A ``laser tape measure`` for measuring distance is disclosed which includes a transmitter such as a laser diode which transmits a sequence of electromagnetic pulses in response to a transmit timing signal. A receiver samples reflections from objects within the field of the sequence of visible electromagnetic pulses with controlled timing, in response to a receive timing signal. The receiver generates a sample signal in response to the samples which indicates distance to the object causing the reflections. The timing circuit supplies the transmit timing signal to the transmitter and supplies the receive timing signal to the receiver. The receive timing signal causes the receiver to sample the reflection such that the time between transmission of pulses in the sequence in sampling by the receiver sweeps over a range of delays. The transmit timing signal causes the transmitter to transmit the sequence of electromagnetic pulses at a pulse repetition rate, and the received timing signal sweeps over the range of delays in a sweep cycle such that reflections are sampled at the pulse repetition rate and with different delays in the range of delays, such that the sample signal represents received reflections in equivalent time. The receiver according to one aspect of the invention includes an avalanche photodiode and a sampling gate coupled to the photodiode which is responsive to the received timing signal. The transmitter includes a laser diode which supplies a sequence of visible electromagnetic pulses. A bright spot projected on to the target clearly indicates the point that is being measured, and the user can read the range to that point with precision of better than 0.1%. 7 figs.

  14. Photometric Passive Range Sensor

    NASA Astrophysics Data System (ADS)

    Argueta-Diaz, Victor; García-Valenzuela, Augusto

    2008-04-01

    In this paper we present a passive optical ranging method that consists of taking several photometric measurements from the light radiated by an object and deriving the range from these measurements. This passive ranging device uses an iris of radius a, a lens of radius larger than a, and a photodetector of radius p

  15. Front Range Report, Abstracts

    NASA Astrophysics Data System (ADS)

    Spence, William

    The second regional conference of the Front Range Branch, AGU, was attended by more than 80 professionals and some 20 outstanding high school students. The conference included 2 days of interdisciplinary talks, and lots of discussion, that primarily were keyed to geophysical studies of Colorado, Wyoming, and New Mexico. Other talks reported on nonregional, and sometimes global, studies being done by geophypsicists of the Front Range region.Topics included tectonics of the Front Range and the Colorado Plateau, pollution of the Arkansas and Mississippi rivers, and a supreme polluting event that caused the late-Cretaceous extinctions. Other notable talks were on toxic cleanup, microburst (wind shear) detection at U.S. airports, and other meteorological studies. Several talks treated the audience to the excitement of new work and surprise discoveries. The meeting was multimedia, including the playing of two videos through a projection TV and the playing of a fascinating tape between an airport control tower and incoming pilots during a severe microburst event.

  16. On effective dose for radiotherapy based on doses to nontarget organs and tissues.

    PubMed

    Uselmann, Adam J; Thomadsen, Bruce R

    2015-02-01

    The National Council for Radiation Protection and Measurement (NCRP) published estimates for the collective population dose and the mean effective dose to the population of the United States from medical imaging procedures for 1980/1982 and for 2006. The earlier report ignored the effective dose from radiotherapy and the latter gave a cursory discussion of the topic but again did not include it in the population exposure for various reasons. This paper explains the methodology used to calculate the effective dose in due to radiotherapy procedures in the latter NCRP report and revises the values based on more detailed modeling. This study calculated the dose to nontarget organs from radiotherapy for reference populations using CT images and published peripheral dose data. Using International Commission on Radiological Protection (ICRP) 60 weighting factors, the total effective dose to nontarget organs in radiotherapy patients is estimated as 298 ± 194 mSv per patient, while the U.S. population effective dose is 0.939 ± 0.610 mSv per person, with a collective dose of 283,000 ± 184,000 person Sv per year. Using ICRP 103 weighting factors, the effective dose is 281 ± 183 mSv per patient, 0.887 ± 0.577 mSv per person in the U.S., and 268,000 ± 174,000 person Sv per year. The uncertainty in the calculations is largely governed by variations in patient size, which was accounted for by considering a range of patient sizes and taking the average treatment site to nontarget organ distance. The methods used to estimate the effective doses from radiotherapy used in NCRP Report No. 160 have been explained and the values updated.

  17. On effective dose for radiotherapy based on doses to nontarget organs and tissues

    SciTech Connect

    Uselmann, Adam J. Thomadsen, Bruce R.

    2015-02-15

    Purpose: The National Council for Radiation Protection and Measurement (NCRP) published estimates for the collective population dose and the mean effective dose to the population of the United States from medical imaging procedures for 1980/1982 and for 2006. The earlier report ignored the effective dose from radiotherapy and the latter gave a cursory discussion of the topic but again did not include it in the population exposure for various reasons. This paper explains the methodology used to calculate the effective dose in due to radiotherapy procedures in the latter NCRP report and revises the values based on more detailed modeling. Methods: This study calculated the dose to nontarget organs from radiotherapy for reference populations using CT images and published peripheral dose data. Results: Using International Commission on Radiological Protection (ICRP) 60 weighting factors, the total effective dose to nontarget organs in radiotherapy patients is estimated as 298 ± 194 mSv per patient, while the U.S. population effective dose is 0.939 ± 0.610 mSv per person, with a collective dose of 283 000 ± 184 000 person Sv per year. Using ICRP 103 weighting factors, the effective dose is 281 ± 183 mSv per patient, 0.887 ± 0.577 mSv per person in the U.S., and 268 000 ± 174 000 person Sv per year. The uncertainty in the calculations is largely governed by variations in patient size, which was accounted for by considering a range of patient sizes and taking the average treatment site to nontarget organ distance. Conclusions: The methods used to estimate the effective doses from radiotherapy used in NCRP Report No. 160 have been explained and the values updated.

  18. Validation of the photon dose calculation model in the VARSKIN 4 skin dose computer code.

    PubMed

    Sherbini, Sami; Decicco, Joseph; Struckmeyer, Richard; Saba, Mohammad; Bush-Goddard, Stephanie

    2012-12-01

    An updated version of the skin dose computer code VARSKIN, namely VARSKIN 4, was examined to determine the accuracy of the photon model in calculating dose rates with different combinations of source geometry and radionuclides. The reference data for this validation were obtained by means of Monte Carlo transport calculations using MCNP5. The geometries tested included the zero volume sources point and disc, as well as the volume sources sphere and cylinder. Three geometries were tested using source directly on the skin, source off the skin with an absorber material between source and skin, and source off the skin with only an air gap between source and skin. The results of these calculations showed that the non-volume sources produced dose rates that were in very good agreement with the Monte Carlo calculations, but the volume sources resulted in overestimates of the dose rates compared with the Monte Carlo results by factors that ranged up to about 2.5. The results for the air gap showed poor agreement with Monte Carlo for all source geometries, with the dose rates overestimated in all cases. The conclusion was that, for situations where the beta dose is dominant, these results are of little significance because the photon dose in such cases is generally a very small fraction of the total dose. For situations in which the photon dose is dominant, use of the point or disc geometries should be adequate in most cases except those in which the dose approaches or exceeds an applicable limit. Such situations will often require a more accurate dose assessment and may require the use of methods such as Monte Carlo transport calculations.

  19. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  20. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  1. Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

    PubMed

    Duong, Phuong-Anh; Little, Brent P

    2014-08-01

    Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

    NASA Astrophysics Data System (ADS)

    Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

    2017-03-01

    This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (p<0.01). The breast dose was reduced by 30+/-2%. For h factors, organs in the anterior region (e.g. thyroid, stomach) exhibited substantial decreases, and the medial, distributed, and posterior region either saw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

  3. Measurement of dose in panoramic dental radiology.

    PubMed

    Williams, J R; Montgomery, A

    2000-09-01

    The National Radiological Protection Board (NRPB) has recommended the introduction of dose-width product (DWP) for the measurement of patient dose in panoramic dental radiology and has proposed a reference level of 65 mGy mm for adult exposures. This paper describes a method for measuring DWP and dose-area product (DAP) using thermoluminescent dosemeters (TLDs). The technique was used on 16 sets with a range of exposure settings. The mean value of DWP was 14% higher than the mean value reported from a survey by the NRPB. This difference is most likely to be caused by systematic variations due to measurement method. The average DAP for a standard adult examination was shown to be 11.3 cGy cm2. Data are presented so that the DAP can be derived from the exposure factors (tube current and operating potential) and beam area. Based on published data for effective dose, it is estimated that the DAP to effective dose conversion factor is approximately 0.06 mSv(Gy cm2)-1. The average DAP value (11.3 cGy cm2) can be compared with the average value for intraoral radiography (9.3 cGy cm2) based on the NRPB survey of entrance surface doses assuming 6 cm circular collimation.

  4. Occupational dose constraints in interventional cardiology procedures: the DIMOND approach

    NASA Astrophysics Data System (ADS)

    Tsapaki, Virginia; Kottou, Sophia; Vano, Eliseo; Komppa, Tuomo; Padovani, Renato; Dowling, Annita; Molfetas, Michael; Neofotistou, Vassiliki

    2004-03-01

    Radiation fields involved in angiographic suites are most uneven with intensity and gradient varying widely with projection geometry. The European Commission DIMOND III project addressed among others, the issues regarding optimization of staff doses with an attempt to propose preliminary occupational dose constraints. Two thermoluminescent dosemeters (TLD) were used to assess operators' extremity doses (left shoulder and left foot) during 20 coronary angiographies (CAs) and 20 percutaneous transluminal coronary angioplasties (PTCAs) in five European centres. X-ray equipment, radiation protection measures used and the dose delivered to the patient in terms of dose-area product (DAP) were recorded so as to subsequently associate them with operator's dose. The range of staff doses noted for the same TLD position, centre and procedure type emphasizes the importance of protective measures and technical characteristics of x-ray equipment. Correlation of patient's DAP with staff shoulder dose is moderate whereas correlation of patient's DAP with staff foot dose is poor in both CA and PTCA. Therefore, it is difficult to predict operator's dose from patient's DAP mainly due to the different use of protective measures. A preliminary occupational dose constraint value was defined by calculating cardiologists' annual effective dose and found to be 0.6 mSv.

  5. Pharmacokinetics and dose proportionality of ceftibuten in men.

    PubMed Central

    Lin, C; Lim, J; Radwanski, E; Marco, A; Affrime, M

    1995-01-01

    The pharmacokinetics and dose proportionality of ceftibuten were evaluated in healthy male volunteers receiving single oral doses of 200, 400, and 800 mg of ceftibuten. The drug was absorbed with similar times to the maximum concentration of drug in plasma for all three doses. Concentrations of ceftibuten in plasma increased with increasing dose. Analysis of variance was carried out on the dose-adjusted values for the maximum concentration of drug in plasma and the area under the plasma concentration-time curve; the results indicated that the concentrations in plasma after the 200- and 400-mg doses were dose proportional, and after the 800-mg of dose they were less than dose proportional. The elimination half-life from plasma ranged from 2.0 to 2.3 h and was independent of dose. The total excretion of unchanged ceftibuten in urine accounted for 53 to 68% of the dose, and the renal clearance was estimated to be 53 to 61 ml/min after all doses. The amount of ceftibuten-trans, the major in vitro and in vivo conversion product of ceftibuten, was low in both plasma and urine. PMID:7726498

  6. Laser Range Camera Modeling

    SciTech Connect

    Storjohann, K.

    1990-01-01

    This paper describes an imaging model that was derived for use with a laser range camera (LRC) developed by the Advanced Intelligent Machines Division of Odetics. However, this model could be applied to any comparable imaging system. Both the derivation of the model and the determination of the LRC's intrinsic parameters are explained. For the purpose of evaluating the LRC's extrinsic parameters, i.e., its external orientation, a transformation of the LRC's imaging model into a standard camera's (SC) pinhole model is derived. By virtue of this transformation, the evaluation of the LRC's external orientation can be found by applying any SC calibration technique.

  7. Radiation dose-reduction strategies in thoracic CT.

    PubMed

    Moser, J B; Sheard, S L; Edyvean, S; Vlahos, I

    2017-05-01

    Modern computed tomography (CT) machines have the capability to perform thoracic CT for a range of clinical indications at increasingly low radiation doses. This article reviews several factors, both technical and patient-related, that can affect radiation dose and discusses current dose-reduction methods relevant to thoracic imaging through a review of current techniques in CT acquisition and image reconstruction. The fine balance between low radiation dose and high image quality is considered throughout, with an emphasis on obtaining diagnostic quality imaging at the lowest achievable radiation dose. The risks of excessive radiation dose reduction are also considered. Inappropriately low dose may result in suboptimal or non-diagnostic imaging that may reduce diagnostic confidence, impair diagnosis, or result in repeat examinations incurring incremental ionising radiation exposure. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  8. Growth control of Saccharomyces cerevisiae through dose of oxygen atoms

    NASA Astrophysics Data System (ADS)

    Hashizume, Hiroshi; Ohta, Takayuki; Hori, Masaru; Ito, Masafumi

    2015-08-01

    To investigate the dose-dependent effects of neutral oxygen radicals on the proliferation as well as the inactivation of microorganisms, we treated suspensions of budding yeast cells with oxygen radicals using an atmospheric-pressure oxygen radical source, varying the fluxes of O(3Pj) from 1.3 × 1016 to 2.3 × 1017 cm-2 s-1. Proliferation was promoted at doses of O(3Pj) ranging from 6 × 1016 to 2 × 1017 cm-3, and suppressed at doses ranging from 3 × 1017 to 1 × 1018 cm-3; cells were inactivated by O(3Pj) doses exceeding 1 × 1018 cm-3, even when the flux was varied over the above flux range. These results showed that the growth of cells was regulated primarily in response to the total dose of O(3Pj).

  9. Volumetric (3D) bladder dose parameters are more reproducible than point (2D) dose parameters in vaginal vault high-dose-rate brachytherapy

    PubMed Central

    Sapienza, Lucas Gomes; Flosi, Adriana; Aiza, Antonio; de Assis Pellizzon, Antonio Cassio; Chojniak, Rubens; Baiocchi, Glauco

    2016-01-01

    There is no consensus on the use of computed tomography in vaginal cuff brachytherapy (VCB) planning. The purpose of this study was to prospectively determine the reproducibility of point bladder dose parameters (DICRU and maximum dose), compared with volumetric-based parameters. Twenty-two patients who were treated with high-dose-rate (HDR) VCB underwent simulation by computed tomography (CT-scan) with a Foley catheter at standard tension (position A) and extra tension (position B). CT-scan determined the bladder ICRU dose point in both positions and compared the displacement and recorded dose. Volumetric parameters (D0.1cc, D1.0cc, D2.0cc, D4.0cc and D50%) and point dose parameters were compared. The average spatial shift in ICRU dose point in the vertical, longitudinal and lateral directions was 2.91 mm (range: 0.10–9.00), 12.04 mm (range: 4.50–24.50) and 2.65 mm (range: 0.60–8.80), respectively. The DICRU ratio for positions A and B was 1.64 (p < 0.001). Moreover, a decrease in Dmax was observed (p = 0.016). Tension level of the urinary catheter did not affect the volumetric parameters. Our data suggest that point parameters (DICRU and Dmax) are not reproducible and are not the ideal choice for dose reporting. PMID:27296459

  10. Uncertainties on lung doses from inhaled plutonium.

    PubMed

    Puncher, Matthew; Birchall, Alan; Bull, Richard K

    2011-10-01

    In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

  11. Dose estimates from the Chernobyl accident

    SciTech Connect

    Lange, R.; Dickerson, M.H.; Gudiksen, P.H.

    1987-11-01

    The Lawrence Livermore National Laboratory Atmospheric Release Advisory Capability (ARAC) responded to the Chernobyl nuclear reactor accident in the Soviet Union by utilizing long-range atmospheric dispersion modeling to estimate the amount of radioactivity released (source term) and the radiation dose distribution due to exposure to the radioactive cloud over Europe and the Northern Hemisphere. In later assessments, after the release of data on the accident by the Soviet Union, the ARAC team used their mesoscale to regional scale model to focus in on the radiation dose distribution within the Soviet Union and the vicinity of the Chernobyl plant. 22 refs., 5 figs., 5 tabs.

  12. Dose estimates from the Chernobyl accident

    SciTech Connect

    Lange, R.; Dickerson, M.H.; Gudiksen, P.H. )

    1988-09-01

    The Lawrence Livermore National Laboratory Atmospheric Release Advisory Capability (ARAC) responded to the Chernobyl nuclear reactor accident in the Soviet Union by utilizing long-range atmospheric dispersion modeling to estimate the amount of radioactivity released (source term) and the radiation dose distribution due to exposure to the radioactive cloud over Europe and the northern hemisphere. In later assessments, after the release of data on the accident by the Soviet Union, the ARAC team used their mesoscale-to-regional-scale model to focus on the radiation dose distribution within the Soviet Union and the vicinity of the Chernobyl plant.

  13. Monocular visual ranging

    NASA Astrophysics Data System (ADS)

    Witus, Gary; Hunt, Shawn

    2008-04-01

    The vision system of a mobile robot for checkpoint and perimeter security inspection performs multiple functions: providing surveillance video, providing high resolution still images, and providing video for semi-autonomous visual navigation. Mid-priced commercial digital cameras support the primary inspection functions. Semi-autonomous visual navigation is a tertiary function whose purpose is to reduce the burden of teleoperation and free the security personnel for their primary functions. Approaches to robot visual navigation require some form of depth perception for speed control to prevent the robot from colliding with objects. In this paper present the initial results of an exploration of the capabilities and limitations of using a single monocular commercial digital camera for depth perception. Our approach combines complementary methods in alternating stationary and moving behaviors. When the platform is stationary, it computes a range image from differential blur in the image stack collected at multiple focus settings. When the robot is moving, it extracts an estimate of range from the camera auto-focus function, and combines this with an estimate derived from angular expansion of a constellation of visual tracking points.

  14. Western Aeronautical Test Range

    NASA Technical Reports Server (NTRS)

    Sakahara, Robert D.

    2008-01-01

    NASA's Western Aeronautical Test Range (WATR) is a network of facilities used to support aeronautical research, science missions, exploration system concepts, and space operations. The WATR resides at NASA's Dryden Flight Research Center located at Edwards Air Force Base, California. The WATR is a part of NASA's Corporate Management of Aeronautical Facilities and funded by the Strategic Capability Asset Program (SCAP). It is managed by the Aeronautics Test Program (ATP) of the Aeronautics Research Mission Directorate (ARMD) to provide the right facility at the right time. NASA is a tenant on Edwards Air Force Base and has an agreement with the Air Force Flight Test Center to use the land and airspace controlled by the Department of Defense (DoD). The topics include: 1) The WATR supports a variety of vehicles; 2) Dryden shares airspace with the AFFTC; 3) Restricted airspace, corridors, and special use areas are available for experimental aircraft; 4) WATR Products and Services; 5) WATR Support Configuration; 6) Telemetry Tracking; 7) Time Space Positioning; 8) Video; 9) Voice Communication; 10) Mobile Operations Facilities; 11) Data Processing; 12) Mission Control Center; 13) Real-Time Data Analysis; and 14) Range Safety.

  15. Range Process Simulation Tool

    NASA Technical Reports Server (NTRS)

    Phillips, Dave; Haas, William; Barth, Tim; Benjamin, Perakath; Graul, Michael; Bagatourova, Olga

    2005-01-01

    Range Process Simulation Tool (RPST) is a computer program that assists managers in rapidly predicting and quantitatively assessing the operational effects of proposed technological additions to, and/or upgrades of, complex facilities and engineering systems such as the Eastern Test Range. Originally designed for application to space transportation systems, RPST is also suitable for assessing effects of proposed changes in industrial facilities and large organizations. RPST follows a model-based approach that includes finite-capacity schedule analysis and discrete-event process simulation. A component-based, scalable, open architecture makes RPST easily and rapidly tailorable for diverse applications. Specific RPST functions include: (1) definition of analysis objectives and performance metrics; (2) selection of process templates from a processtemplate library; (3) configuration of process models for detailed simulation and schedule analysis; (4) design of operations- analysis experiments; (5) schedule and simulation-based process analysis; and (6) optimization of performance by use of genetic algorithms and simulated annealing. The main benefits afforded by RPST are provision of information that can be used to reduce costs of operation and maintenance, and the capability for affordable, accurate, and reliable prediction and exploration of the consequences of many alternative proposed decisions.

  16. MiniAERCam Ranging

    NASA Technical Reports Server (NTRS)

    Talley, Tom

    2003-01-01

    Johnson Space Center (JSC) is designing a small, remotely controlled vehicle that will carry two color and one black and white video cameras in space. The device will launch and retrieve from the Space Vehicle and be used for remote viewing. Off the shelf cellular technology is being used as the basis for communication system design. Existing plans include using multiple antennas to make simultaneous estimates of the azimuth of the MiniAERCam from several sites on the Space Station and use triangulation to find the location of the device. Adding range detection capability to each of the nodes on the Space Vehicle would allow an estimate of the location of the MiniAERCam to be made at each Communication And Telemetry Box (CATBox) independent of all the other communication nodes. This project will investigate the techniques used by the Global Positioning System (GPS) to achieve accurate positioning information and adapt those strategies that are appropriate to the design of the CATBox range determination system.

  17. Small dose... big poison.

    PubMed

    Braitberg, George; Oakley, Ed

    2010-11-01

    It is not possible to identify all toxic substances in a single journal article. However, there are some exposures that in small doses are potentially fatal. Many of these exposures are particularly toxic to children. Using data from poison control centres, it is possible to recognise this group of exposures. This article provides information to assist the general practitioner to identify potential toxic substance exposures in children. In this article the authors report the signs and symptoms of toxic exposures and identify the time of onset. Where clear recommendations on the period of observation and known fatal dose are available, these are provided. We do not discuss management or disposition, and advise readers to contact the Poison Information Service or a toxicologist for this advice.

  18. A mathematical approach to optimal selection of dose values in the additive dose method of ERP dosimetry

    SciTech Connect

    Hayes, R.B.; Haskell, E.H.; Kenner, G.H.

    1996-01-01

    Additive dose methods commonly used in electron paramagnetic resonance (EPR) dosimetry are time consuming and labor intensive. We have developed a mathematical approach for determining optimal spacing of applied doses and the number of spectra which should be taken at each dose level. Expected uncertainitites in the data points are assumed to be normally distributed with a fixed standard deviation and linearity of dose response is also assumed. The optimum spacing and number of points necessary for the minimal error can be estimated, as can the likely error in the resulting estimate. When low doses are being estimated for tooth enamel samples the optimal spacing is shown to be a concentration of points near the zero dose value with fewer spectra taken at a single high dose value within the range of known linearity. Optimization of the analytical process results in increased accuracy and sample throughput.

  19. Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: low doses induce hypolocomotion.

    PubMed

    Singh, Rana A K; Kosten, Therese A; Kinsey, Berma M; Shen, Xiaoyun; Lopez, Angel Y; Kosten, Thomas R; Orson, Frank M

    2012-12-01

    The overall goal of the present study was to determine the effects of different doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four experiments were designed to test a wide range of meth doses in BALB/c female mice. In Experiment 1, we examined locomotor activity induced by an acute administration of low doses of meth (0.01 and 0.03mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3-10mg/kg). In Experiment 3, separate sets of mice were pre-treated with various meth doses once or twice (one injection/week) prior to a locomotor challenge with a low meth dose. Finally, in Experiment 4, we tested whether locomotor activation would be affected by pretreatment with a low or moderate dose of meth one month prior to the low meth dose challenge. Results show that low doses of meth induce hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior exposure to either one moderate or high dose of meth or to two, low doses of meth attenuated the hypolocomotor effect of a low meth dose one week later. This effect was also attenuated in mice tested one month after administration of a moderate meth dose. These results show that low and high doses of meth can have opposing effects on locomotor activity. Further, prior exposure to the drug leads to tolerance, rather than sensitization, of the hypolocomotor response to low meth doses. Published by Elsevier Inc.

  20. Range imaging laser radar

    DOEpatents

    Scott, M.W.

    1990-06-19

    A laser source is operated continuously and modulated periodically (typically sinusoidally). A receiver imposes another periodic modulation on the received optical signal, the modulated signal being detected by an array of detectors of the integrating type. Range to the target determined by measuring the phase shift of the intensity modulation on the received optical beam relative to a reference. The receiver comprises a photoemitter for converting the reflected, periodically modulated, return beam to an accordingly modulated electron stream. The electron stream is modulated by a local demodulation signal source and subsequently converted back to a photon stream by a detector. A charge coupled device (CCD) array then averages and samples the photon stream to provide an electrical signal in accordance with the photon stream. 2 figs.

  1. Range imaging laser radar

    DOEpatents

    Scott, Marion W.

    1990-01-01

    A laser source is operated continuously and modulated periodically (typicy sinusoidally). A receiver imposes another periodic modulation on the received optical signal, the modulated signal being detected by an array of detectors of the integrating type. Range to the target determined by measuring the phase shift of the intensity modulation on the received optical beam relative to a reference. The receiver comprises a photoemitter for converting the reflected, periodically modulated, return beam to an accordingly modulated electron stream. The electron stream is modulated by a local demodulation signal source and subsequently converted back to a photon stream by a detector. A charge coupled device (CCD) array then averages and samples the photon stream to provide an electrical signal in accordance with the photon stream.

  2. Estimation of the Dose and Dose Rate Effectiveness Factor

    NASA Technical Reports Server (NTRS)

    Chappell, L.; Cucinotta, F. A.

    2013-01-01

    Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

  3. Pharmacokinetics of BILR 355 after Multiple Oral Doses Coadministered with a Low Dose of Ritonavir ▿

    PubMed Central

    Huang, Fenglei; Drda, Kristin; MacGregor, Thomas R.; Scherer, Joseph; Rowland, Lois; Nguyen, Thuy; Ballow, Charles; Castles, Mark; Robinson, Patrick

    2009-01-01

    The pharmacokinetics and safety of BILR 355 following oral repeated dosing coadministered with low doses of ritonavir (RTV) were investigated in 12 cohorts of healthy male volunteers with a ratio of 6 to 2 for BILR 355 versus the placebo. BILR 355 was given once a day (QD) coadministered with 100 mg RTV (BILR 355/r) at 5 to 50 mg in a polyethylene glycol solution or at 50 to 250 mg as tablets. BILR 355 tablets were also dosed at 150 mg twice a day (BID) coadministered with 100 mg RTV QD or BID. Following oral dosing, BILR 355 was rapidly absorbed, with the mean time to maximum concentration of drug in serum reached within 1.3 to 5 h and a mean half-life of 16 to 20 h. BILR 355 exhibited an approximately linear pharmacokinetics for doses of 5 to 50 mg when given as a solution; in contrast, when given as tablets, BILR 355 displayed a dose-proportional pharmacokinetics, with a dose range of 50 to 100 mg; from 100 to 150 mg, a slightly downward nonlinear pharmacokinetics occurred. The exposure to BILR 355 was maximized at 150 mg and higher due to a saturated dissolution/absorption process. After oral dosing of BILR 355/r, 150/100 mg BID, the values for the maximum concentration of drug in plasma at steady state, the area under the concentration-time curve from 0 to the dose interval at steady state, and the minimum concentration of drug in serum at steady state were 1,500 ng/ml, 12,500 h·ng/ml, and 570 ng/ml, respectively, providing sufficient suppressive concentration toward human immunodeficiency virus type 1. Based on pharmacokinetic modeling along with the in vitro virologic data, several BILR 355 doses were selected for phase II trials using Monte Carlo simulations. Throughout the study, BILR 355 was safe and well tolerated. PMID:18955519

  4. Cognitive performance in methadone maintenance patients: Effects of time relative to dosing and maintenance dose level

    PubMed Central

    Rass, Olga; Kleykamp, Bethea A.; Vandrey, Ryan G.; Bigelow, George E.; Leoutsakos, Jeannie-Marie; Stitzer, Maxine L.; Strain, Eric; Copersino, Marc L.; Mintzer, Miriam Z.

    2014-01-01

    Given the long-term nature of methadone maintenance treatment, it is important to assess the extent of cognitive side effects. This study investigated cognitive and psychomotor performance in fifty-one methadone maintenance patients (MMP) as a function of time since last methadone dose and maintenance dose level. MMP maintained on doses ranging from 40 to 200 mg (Mean = 97 mg) completed a battery of psychomotor and cognitive measures across two sessions, during peak and trough states, in a double-blind crossover design. Peak sessions were associated with worse performance on measures of sensory processing, psychomotor speed, divided attention, and working memory, compared to trough sessions. The effects of maintenance dose were mixed, with higher dose resulting in worse performance on aspects of attention and working memory, improved performance on executive function, and no effects on several measures. Longer treatment duration was associated with better performance on some measures, but was also associated with increased sensitivity to time since last dose (i.e., worse performance at peak vs. trough) on some measures. The results suggest that cognitive functioning can fluctuate as a function of time since last dose even in MMP who have been maintained on stable doses for an extended time (mean duration in treatment = 4 years), but worsened performance at peak is limited to a subset of functions and may not be clinically significant at these modest levels of behavioral effect. For patients on stable methadone maintenance doses, maintenance at higher doses may not significantly increase the risk of performance impairment. PMID:24548244

  5. Dose esclation in radioimmunotherapy based on projected whole body dose

    SciTech Connect

    Wahl, R.L.; Kaminski, M.S.; Regan, D.

    1994-05-01

    A variety of approaches have been utilized in conducting phase I radioimmunotherapy dose-escalation trials. Escalation of dose has been based on graded increases in administered mCi; mCi/kg; or mCi/m2. It is also possible to escalate dose based on tracer-projected marrow, blood or whole body radiation dose. We describe our results in performing a dose-escalation trial in patients with non-Hodgkin lymphoma based on escalating administered whole-body radiation dose. The mCi dose administered was based on a patient-individualized tracer projected whole-body dose. 25 patients were entered on the study. RIT with 131 I anti-B-1 was administered to 19 patients. The administered dose was prescribed based on the projected whole body dose, determined from patient-individualized tracer studies performed prior to RIT. Whole body dose estimates were based on the assumption that the patient was an ellipsoid, with 131 antibody kinetics determined using a whole-body probe device acquiring daily conjugate views of 1 minute duration/view. Dose escalation levels proceeded with 10 cGy increments from 25 cGy whole-body and continues, now at 75 cGy. The correlation among potential methods of dose escalation and toxicity was assessed. Whole body radiation dose by probe was strongly correlated with the blood radiation dose determined from sequential blood sampling during tracer studies (r=.87). Blood radiation dose was very weakly correlated with mCi dose (r=.4) and mCi/kg (r=.45). Whole body radiation dose appeared less well-correlated with injected dose in mCi (r=.6), or mCi/kg (r=.64). Toxicity has been infrequent in these patients, but appears related to increasing whole body dose. Non-invasive determination of whole-body radiation dose by gamma probe represents a non-invasive method of estimating blood radiation dose, and thus of estimating bone marrow radiation dose.

  6. Comparison of planned and measured rectal dose in-vivo during high dose rate Cobalt-60 brachytherapy of cervical cancer.

    PubMed

    Zaman, Z K; Ung, N M; Malik, R A; Ho, G F; Phua, V C E; Jamalludin, Z; Baharuldin, M T H; Ng, K H

    2014-12-01

    Cobalt-60 (Co-60) is a relatively new source for the application of high-dose rate (HDR) brachytherapy. Radiation dose to the rectum is often a limiting factor in achieving the full prescribed dose to the target during brachytherapy of cervical cancer. The aim of this study was to measure radiation doses to the rectum in-vivo during HDR Co-60 brachytherapy. A total of eleven HDR brachytherapy treatments of cervical cancer were recruited in this study. A series of diodes incorporated in a rectal probe was inserted into the patient's rectum during each brachytherapy procedure. Real-time measured rectal doses were compared to calculated doses by the treatment planning system (TPS). The differences between calculated and measured dose ranged from 8.5% to 41.2%. This corresponds to absolute dose differences ranging from 0.3 Gy to 1.5 Gy. A linear relationship was observed between calculated and measured doses with linear regression R(2) value of 0.88, indicating close association between the measured and calculated doses. In general, absorbed doses for the rectum as calculated by TPS were observed to be higher than the doses measured using the diode probe. In-vivo dosimetry is an important quality assurance method for HDR brachytherapy of cervical cancer. It provides information that can contribute to the reduction of errors and discrepancies in dose delivery. Our study has shown that in-vivo dosimetry is feasible and can be performed to estimate the dose to the rectum during HDR brachytherapy using Co-60.

  7. Brachytherapy source characterization for improved dose calculations using primary and scatter dose separation.

    PubMed

    Russell, Kellie R; Tedgren, Asa K Carlsson; Ahnesjö, Anders

    2005-09-01

    In brachytherapy, tissue heterogeneities, source shielding, and finite patient/phantom extensions affect both the primary and scatter dose distributions. The primary dose is, due to the short range of secondary electrons, dependent only on the distribution of material located on the ray line between the source and dose deposition site. The scatter dose depends on both the direct irradiation pattern and the distribution of material in a large volume surrounding the point of interest, i.e., a much larger volume must be included in calculations to integrate many small dose contributions. It is therefore of interest to consider different methods for the primary and the scatter dose calculation to improve calculation accuracy with limited computer resources. The algorithms in present clinical use ignore these effects causing systematic dose errors in brachytherapy treatment planning. In this work we review a primary and scatter dose separation formalism (PSS) for brachytherapy source characterization to support separate calculation of the primary and scatter dose contributions. We show how the resulting source characterization data can be used to drive more accurate dose calculations using collapsed cone superposition for scatter dose calculations. Two types of source characterization data paths are used: a direct Monte Carlo simulation in water phantoms with subsequent parameterization of the results, and an alternative data path built on processing of AAPM TG43 formatted data to provide similar parameter sets. The latter path is motivated of the large amounts of data already existing in the TG43 format. We demonstrate the PSS methods using both data paths for a clinical 192Ir source. Results are shown for two geometries: a finite but homogeneous water phantom, and a half-slab consisting of water and air. The dose distributions are compared to results from full Monte Carlo simulations and we show significant improvement in scatter dose calculations when the collapsed

  8. Brachytherapy source characterization for improved dose calculations using primary and scatter dose separation

    SciTech Connect

    Russell, Kellie R.; Carlsson Tedgren, Aasa K.; Ahnesjoe, Anders

    2005-09-15

    In brachytherapy, tissue heterogeneities, source shielding, and finite patient/phantom extensions affect both the primary and scatter dose distributions. The primary dose is, due to the short range of secondary electrons, dependent only on the distribution of material located on the ray line between the source and dose deposition site. The scatter dose depends on both the direct irradiation pattern and the distribution of material in a large volume surrounding the point of interest, i.e., a much larger volume must be included in calculations to integrate many small dose contributions. It is therefore of interest to consider different methods for the primary and the scatter dose calculation to improve calculation accuracy with limited computer resources. The algorithms in present clinical use ignore these effects causing systematic dose errors in brachytherapy treatment planning. In this work we review a primary and scatter dose separation formalism (PSS) for brachytherapy source characterization to support separate calculation of the primary and scatter dose contributions. We show how the resulting source characterization data can be used to drive more accurate dose calculations using collapsed cone superposition for scatter dose calculations. Two types of source characterization data paths are used: a direct Monte Carlo simulation in water phantoms with subsequent parameterization of the results, and an alternative data path built on processing of AAPM TG43 formatted data to provide similar parameter sets. The latter path is motivated of the large amounts of data already existing in the TG43 format. We demonstrate the PSS methods using both data paths for a clinical {sup 192}Ir source. Results are shown for two geometries: a finite but homogeneous water phantom, and a half-slab consisting of water and air. The dose distributions are compared to results from full Monte Carlo simulations and we show significant improvement in scatter dose calculations when the

  9. Dosimetric evaluation of the OneDose MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures

    SciTech Connect

    Ding, George X.; Coffey, Charles W.

    2010-09-15

    Purpose: The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. Methods: The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). Results: The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. Conclusions: The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

  10. Health benefits from low-dose irradiation

    SciTech Connect

    Luckey, T.D.

    1996-12-31

    Whole-body exposures of mice and humans show no harm from low doses of ionizing radiation. Forty reports show statistically significant, p < 0.01, beneficial effects when cancer and total mortality rates were examined in mice. In vitro experiments indicate that radiogenic metabolism, adaptive repair mechanisms, such as DNA repair enzymes, and the essential nature of ionizing radiation are responsible for part of this activity. However, overwhelming evidence shows that low-dose irradiation increases immune competence. Such data negate the linear concept, which has no reliable whole-animal data to support it in the low-dose range. Cell culture data are not pertinent; such cells do not have a complete immune system.

  11. Uncertainty Quantification in Internal Dose Calculations for Seven Selected Radiopharmaceuticals.

    PubMed

    Spielmann, Vladimir; Li, Wei Bo; Zankl, Maria; Oeh, Uwe; Hoeschen, Christoph

    2016-01-01

    Dose coefficients of radiopharmaceuticals have been published by the International Commission on Radiological Protection (ICRP) and the MIRD Committee but without information concerning uncertainties. The uncertainty information of dose coefficients is important, for example, to compare alternative diagnostic methods and choose the method that causes the lowest patient exposure with appropriate and comparable diagnostic quality. For the study presented here, an uncertainty analysis method was developed and used to calculate the uncertainty of the internal doses of 7 common radiopharmaceuticals. On the basis of the generalized schema of dose calculation recommended by the ICRP and MIRD Committee, an analysis based on propagation of uncertainty was developed and applied for 7 radiopharmaceuticals. The method takes into account the uncertainties contributed from pharmacokinetic models and the so-called S values derived from several voxel computational phantoms previously developed at Helmholtz Zentrum München. Random and Latin hypercube sampling techniques were used to sample parameters of pharmacokinetic models and S values, and the uncertainties of absorbed doses and effective doses were calculated. The uncertainty factors (square root of the ratio between 97.5th and 2.5th percentiles) for organ-absorbed doses are in the range of 1.1-3.3. Uncertainty values of effective doses are lower in comparison to absorbed doses, the maximum value being approximately 1.4. The ICRP reference values showed a deviation comparable to the effective dose calculated in this study. A general statistical method was developed for calculating the uncertainty of absorbed doses and effective doses for 7 radiopharmaceuticals. The dose uncertainties can be used to further identify the most important parameters in the dose calculation and provide reliable dose coefficients for risk analysis of the patients in nuclear medicine. © 2016 by the Society of Nuclear Medicine and Molecular Imaging

  12. Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV).

    PubMed

    McKenney, Douglas G; Kurath, Gael; Wargo, Andrew R

    2016-03-02

    The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50 values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

  13. Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

    USGS Publications Warehouse

    McKenney, Douglas; Kurath, Gael; Wargo, Andrew

    2016-01-01

    The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

  14. A Bayesian Semiparametric Model for Radiation Dose-Response Estimation.

    PubMed

    Furukawa, Kyoji; Misumi, Munechika; Cologne, John B; Cullings, Harry M

    2016-06-01

    In evaluating the risk of exposure to health hazards, characterizing the dose-response relationship and estimating acceptable exposure levels are the primary goals. In analyses of health risks associated with exposure to ionizing radiation, while there is a clear agreement that moderate to high radiation doses cause harmful effects in humans, little has been known about the possible biological effects at low doses, for example, below 0.1 Gy, which is the dose range relevant to most radiation exposures of concern today. A conventional approach to radiation dose-response estimation based on simple parametric forms, such as the linear nonthreshold model, can be misleading in evaluating the risk and, in particular, its uncertainty at low doses. As an alternative approach, we consider a Bayesian semiparametric model that has a connected piece-wise-linear dose-response function with prior distributions having an autoregressive structure among the random slope coefficients defined over closely spaced dose categories. With a simulation study and application to analysis of cancer incidence data among Japanese atomic bomb survivors, we show that this approach can produce smooth and flexible dose-response estimation while reasonably handling the risk uncertainty at low doses and elsewhere. With relatively few assumptions and modeling options to be made by the analyst, the method can be particularly useful in assessing risks associated with low-dose radiation exposures.

  15. Treatment outcome for flexible dosing buprenorphine maintenance treatment.

    PubMed

    Fareed, Ayman; Vayalapalli, Sreedevi; Casarella, Jennifer; Drexler, Karen

    2012-03-01

    Achieving the best treatment outcome with the least cost should be the goal for buprenorphine office-based treatment. We conducted an observational retrospective chart review to compare the treatment outcome for patients (n = 56) receiving high dose of buprenorphine (above 16 mg daily) and patients (n = 21) receiving moderate doses (8-16 mg daily). The percentages of the first four urine drug screens (UDS) positive for opiates were significantly higher for the high-dose group than for the moderate-dose group (F = 7.93, df = 7, p < .0001). However, the percentages of the most recent four UDS positive for opiates were not statistically significant (F = .62, df = 7, p = .74). The difference in the percentages of the first and last UDS for the high-dose group showed significant reduction from admission to most recently but there was no significant difference for the moderate-dose group (t = 3.1, df = 105, p = .002 for the high-dose group and t = 1.1, df = 40, p = .27 for the moderate-dose group). Using flexible buprenorphine dosing schedule with the option of titrating the dose up to 32 mg daily may offer better treatment outcome for patients who would not respond to the lower dose range.

  16. Neutron range spectrometer

    DOEpatents

    Manglos, Stephen H.

    1989-06-06

    A neutron range spectrometer and method for determining the neutron energy spectrum of a neutron emitting source are disclosed. Neutrons from the source are collimnated along a collimation axis and a position sensitive neutron counter is disposed in the path of the collimated neutron beam. The counter determines positions along the collimation axis of interactions between the neutrons in the neutron beam and a neutron-absorbing material in the counter. From the interaction positions, a computer analyzes the data and determines the neutron energy spectrum of the neutron beam. The counter is preferably shielded and a suitable neutron-absorbing material is He-3. The computer solves the following equation in the analysis: ##EQU1## where: N(x).DELTA.x=the number of neutron interactions measured between a position x and x+.DELTA.x, A.sub.i (E.sub.i).DELTA.E.sub.i =the number of incident neutrons with energy between E.sub.i and E.sub.i +.DELTA.E.sub.i, and C=C(E.sub.i)=N .sigma.(E.sub.i) where N=the number density of absorbing atoms in the position sensitive counter means and .sigma. (E.sub.i)=the average cross section of the absorbing interaction between E.sub.i and E.sub.i +.DELTA.E.sub.i.

  17. Medical x-ray exposure doses as contaminants of atomic bomb doses

    SciTech Connect

    Yamamoto, O.; Antoku, S.; Russell, W.J.; Fujita, S.; Sawada, S.

    1988-03-01

    Since 1967 at the times of their biennial ABCC/RERF radiological examinations, all Adult Health Study (AHS) subjects have been interviewed to determine the exposures to medical x-rays they experienced in institutions other than RERF in order to estimate the numbers of examinations and corresponding doses which they received. These data have been stored on computer tapes together with the doses these subjects received during their radiological examinations in the ABCC/RERF Department of Radiology. Thus, their medical x-ray doses are available along with their atomic bomb doses (tentative 1965 doses revised, T65DR) for assessment of the role of ionizing radiation in the development of diseases. The medical x-ray doses incurred at RERF were assessed by means of phantom dosimetry. Those at other institutions were determined using phantom dosimetry data and results of surveys for trends in radiological examinations in Hiroshima and Nagasaki. By the end of 1982, the average medical x-ray doses to the active bone marrow were 12.04 mGy for A-bomb exposed groups and 8.92 mGy for control groups (not-in-cities); to the male gonads, 2.26 mGy and 1.89 mGy, respectively; and to the female gonads, 17.45 mGy and 12.58 mGy, respectively. Results for Hiroshima and Nagasaki were similar. The main impact of medical x-ray doses was in the lowest T65DR group. Medical x-ray active bone marrow doses ranged from 0.05-500% (mean, 35%) of A-bomb doses in the 10-99 mGy T65DR group. In the 100-999 mGy T65DR group, medical x-ray active bone marrow doses ranged from 0.005-50% (mean, 5%) of their T65DR. In the greater than 1000-mGy T65DR group, medical x-ray exposures were proportionally less. Medical x-ray exposures produced smaller doses to the gonads of males than to those of the females.

  18. Can point doses predict volumetric dose to rectum and bladder: a CT-based planning study in high dose rate intracavitary brachytherapy of cervical carcinoma?

    PubMed Central

    Patil, V M; Patel, F D; Chakraborty, S; Oinam, A S; Sharma, S C

    2011-01-01

    Objective Point doses, as defined by the International Commission on Radiation Units and Measurements (ICRU), are classically used to evaluate doses to the rectum and bladder in high dose rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer. Several studies have shown good correlation between the ICRU point doses and the volumetric doses to these organs. In the present study we attempted to evaluate whether this correlation could be used to predict the volumetric doses to these organs. Methods A total of 150 HDR-ICBT insertions performed between December 2006 and June 2008 were randomly divided into two groups. Group A (n=50) was used to derive the correlation between the point and volumetric doses using regression analysis. This was tested in Group B (n=100) insertions using studentised residuals and Bland–Altman plots. Results Significant correlations were obtained for all volumetric doses and ICRU point doses for rectum and bladder in Group A insertions. The strongest correlation was found for the dose to 2 cc volumes (D2cc). The correlation coefficients for bladder and rectal D2cc versus the respective ICRU point doses were 0.82 and 0.77, respectively (p<0.001). Statistical validation of equations generated in Group B showed mean studentised residual values of 0.001 and 0.000 for the bladder and rectum. However, Bland–Altman analysis showed that the error range for these equations for bladder and rectum were ±64% and ±41% of the point A dose, respectively, which makes these equations unreliable for clinical use. Conclusion Volumetric imaging is essential to obtain proper information about volumetric doses. PMID:21511749

  19. Annoyance caused by shooting range noise

    NASA Astrophysics Data System (ADS)

    Levein, B.; Åhrlin, U.

    1988-12-01

    Noise from shooting ranges is characterized by high levels of impulse noise with a large contribution of low frequencies. The knowledge of human reactions to this kind of noise is as yet incomplete. A questionnaire study was performed around one civilian and three military artillery ranges in order to elucidate the annoyance reactions among nearby residents. The extent of annoyance was determined through postal questionnaires. In a first questionnaire, containing general questions about the residential area, persons "annoyed" by "noise from shooting ranges" were identified. A second questionnaire, distributed only to those annoyed by the noise, contained more detailed questions concerning the annoyance reaction. A total of 299 persons participated in the study. Among the residents in the vicinity of the three artillery ranges, 31-35% reported that they were "very annoyed" by the noise. Corresponding data for the civilian shooting range was 15%. The characteristics of the exposure most frequently reported as the main source of annoyance was "heavy weapons" and "vibrations" in all areas. Furthermore, the annoyance reactions were most frequently experienced in the evening and night hours. Establishment of dose-response relationships was not considered relevant due to the small number of areas studied and the similarity in exposure levels (around 85 dB(A) FAST expressed as peak levels). The results of the study demonstrate that noise from shooting ranges, especially such with a large contribution of heavy weapons, is a potential source of great annoyance. Further studies have been initiated in order to obtain a wider distribution of peak levels which will enable the establishment of dose-response relationships.

  20. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-12-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

  1. Dose-Response—A Challenge for Allelopathy?

    PubMed Central

    Belz, Regina G.; Hurle, Karl; Duke, Stephen O.

    2005-01-01

    The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions. PMID:19330161

  2. Dose-response-a challenge for allelopathy?

    PubMed

    Belz, Regina G; Hurle, Karl; Duke, Stephen O

    2005-04-01

    The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

  3. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  4. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-04-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness. The endpoint which is being utilized is cataractogenesis. The advantages conferred by this system stems primarily from the non-invasive longitudinal analysis which it allows. It also exploits a well defined system and one which has demonstrated sensitivity to the inverse dose rate effect observed with heavy ions. Four week old rats were divided into 8 dose groups which received single or fractionated total doses of .2, 1.0, 5.0 and 25 cGy of monoenergetic 435 keV neutrons. Special restraining jigs were devised to insure that the eye at the midpoint of the lens received the appropriate energy and dose with a relative error of {plus minus} 5%. The fractionated regimen consisted of four exposures, each administered at 3 hour intervals. The reference radiations, 250 kVp X-rays, were administered in the same fashion but in doses ranging from .5 to 6.0 Gy. The animals are examined on a bi-weekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit-lamp Imaging System. The follow-ups will continue throughout the lifespan of the animals. When opacification begins full documentation will involve the Zeiss imaging system and Oxford retroillumination photography. The processing routinely employs the Merriam/Focht scoring system for cross-referencing with previous cataract studies and establish cataractogenecity using a proven scoring method.

  5. National reference doses for dental cephalometric radiography.

    PubMed

    Holroyd, J R

    2011-12-01

    Diagnostic reference levels (DRLs) are an important tool in the optimisation of clinical radiography. Although national DRLs are provided for many diagnostic procedures including dental intra-oral radiography, there are currently no national DRLs set for cephalometric radiography. In the absence of formal national DRLs, the Health Protection Agency (HPA) has previously published National Reference Doses (NRDs) covering a wide range of diagnostic X-ray examinations. The aim of this study was to determine provisional NRDs for cephalometric radiography. Measurements made by the Dental X-ray Protection Service (DXPS) of the HPA, as part of the cephalometric X-ray equipment testing service provided to dentists and dental trade companies throughout the UK, were used to derive provisional NRDs. Dose-area product measurements were made on 42 X-ray sets. Third quartile dose-area product values for adult and child lateral cephalometric radiography were found to be 41 mGy cm² and 25 mGy cm², respectively, with individual measurements ranging from 3 mGy cm² to 108 mGy cm². This report proposes provisional NRDs of 40 mGy cm² and 25 mGy cm² for adult and child lateral cephalometric radiographs, respectively; these doses could be considered by employers when establishing their local DRLs.

  6. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Cannon, S.D.; Finch, S.M.

    1992-10-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.

  7. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1991-01-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source terms; environmental transport environmental monitoring data; demographics, agriculture, food habits; environmental pathways and dose estimates.

  8. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-02-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates.

  9. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S.M.; McMakin, A.H.

    1992-01-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.

  10. Equivalent normalized total dose estimates in cyberknife radiotherapy dose delivery in prostate cancer hypofractionation regimens.

    PubMed

    Sudahar, H; Kurup, P G G; Murali, V; Mahadev, P; Velmurugan, J

    2012-04-01

    As the α/β value of prostate is very small and lower than the surrounding critical organs, hypofractionated radiotherapy became a vital mode of treatment of prostate cancer. Cyberknife (Accuray Inc., Sunnyvale, CA, USA) treatment for localized prostate cancer is performed in hypofractionated dose regimen alone. Effective dose escalation in the hypofractionated regimen can be estimated if the corresponding conventional 2 Gy per fraction equivalent normalized total dose (NTD) distribution is known. The present study aims to analyze the hypofractionated dose distribution of localized prostate cancer in terms of equivalent NTD. Randomly selected 12 localized prostate cases treated in cyberknife with a dose regimen of 36.25 Gy in 5 fractions were considered. The 2 Gy per fraction equivalent NTDs were calculated using the formula derived from the linear quadratic (LQ) model. Dose distributions were analyzed with the corresponding NTDs. The conformity index for the prescribed target dose of 36.25 Gy equivalent to the NTD dose of 90.63 Gy (α/β = 1.5) or 74.31 Gy (α/β = 3) was ranging between 1.15 and 1.73 with a mean value of 1.32 ± 0.15. The D5% of the target was 111.41 ± 8.66 Gy for α/β = 1.5 and 90.15 ± 6.57 Gy for α/β = 3. Similarly, the D95% was 91.98 ± 3.77 Gy for α/β = 1.5 and 75.35 ± 2.88 Gy for α/β = 3. The mean values of bladder and rectal volume receiving the prescribed dose of 36.25 Gy were 0.83 cm3 and 0.086 cm3, respectively. NTD dose analysis shows an escalated dose distribution within the target for low α/β (1.5 Gy) with reasonable sparing of organs at risk. However, the higher α/β of prostate (3 Gy) is not encouraging the fact of dose escalation in cyberknife hypofractionated dose regimen of localized prostate cancer.

  11. Dosing accuracy of commonly used disposable insulin pens.

    PubMed

    Krzywon, M; Abdel-Tawab, M; van der Burg, T; Fuhr, U; Schubert-Zsilavecz, M

    2010-04-01

    The present study aimed to assess the dosing accuracy of commonly used disposable insulin pens including SoloStar (SR)*, FlexPen (FP) dagger, Next Generation FlexPen (NGFP) dagger, and KwikPen (KP) double dagger. It is the first comparative study covering the whole dosing range from 1 U to 60 U. It also covers the accuracy of SR at 80 U. A total of sixty insulin pens from two lots of each pen type were used. From each pen 1 U, 10 U, 30 U, 40 U, 60 U and 80 U were dispensed in random order. The 80 U dose was only evaluated for the SR as the other insulin pens do not deliver this dose in one injection. The actual doses were determined gravimetrically taking density of the different insulin preparations into account. The evaluation of dose accuracy was based on the regulations of the International Organization for Standardization (DIN EN ISO 11608-1:2000). All tested insulin pens met the requirements for accuracy with none of the single values at all dose levels being outside the defined range of the ISO recommendations (1 +/- 1 U, 10 +/- 1 U, 30 +/- 1.5 U, 40 +/- 2 U, 60 +/- 3 U and 80 +/- 4 U). For the investigated dosage levels the absolute average deviation of all insulin pens ranged between 0.09 and 0.81 U. The present study demonstrates an excellent dosing accuracy for all tested insulin pens, with no clinically relevant differences between the products.

  12. A Range-Shift Technique for TOF Range Image Sensors

    NASA Astrophysics Data System (ADS)

    Sawada, Tomonari; Ito, Kana; Nakayama, Masakatsu; Kawahito, Shoji

    In Time-of-Flight (TOF) range image sensors using periodical pulsed light, there is a trade-off between the maximum range and range resolution. This paper proposes a range-shift technique for improving range resolution of the TOF range image sensor without sacrificing the measurement range. The range-shift operation uses a TOF range imaging pixel with periodical charge draining structure and several time-shifted short pulses. The use of the short pulse can improve the range resolution. The range image using the range-shift technique is synthesized with several sub-frames, each acquires one of the shifted range images. The use of the small duty-ratio pulse leads to reducing the effect of ambient light and improving the range resolution. The range-shift technique is tested with an implemented TOF range image sensor and it is found that the range resolution is improved to 2cm using a 10ns light pulse and 7 overlapped shifted ranges for the measurement range of 0.5m to 4.0m.

  13. Ambient dose equivalents in TGFs

    NASA Astrophysics Data System (ADS)

    Celestin, Sebastien; Pincon, Jean-Louis; Trompier, Francois

    2017-04-01

    Terrestrial gamma-ray flashes (TGFs) are bursts of high-energy photons originating from the Earth's atmosphere in association with thunderstorm activity [e.g., Briggs et al., JGR, 118, 3805, 2013]. TGFs are associated with initial propagation stages of intracloud lightning, which represent the most frequent type of lightning discharges [e.g., Cummer et al., GRL, 42, 7792, 2015, and references therein]. TGFs are known to be produced inside common thunderclouds [e.g., Splitt et al., JGR, 115, A00E38, 2010] typically at altitudes ranging from 10 to 14 km [e.g., Cummer et al., GRL, 41, 8586, 2014]. The global TGF occurrence rate is estimated to be 400,000 per year concerning TGFs detectable by Fermi-GBM (Gamma ray Burst Monitor) [Briggs et al., 2013], but detailed analysis of satellite measurements [Østgaard et al., JGR, 117, A03327, 2012] and theoretical studies [Celestin et al., JGR, 120, 10712, 2015] suggest that it cannot be excluded that TGFs represent a part of a regular process taking place during the propagation of lightning discharges. It is important to assess the risk induced by TGFs for airline passengers and crews on board aircraft approaching thunderstorms. Dwyer et al. [JGR, 115, D09206, 2010] have estimated that if an aircraft were to find itself in the source electron beam giving rise to a TGF, passengers and crews might receive effective radiation doses above the regulatory limit depending on the beam diameter. Moreover, Tavani et al. [Nat. Hazards Earth Syst. Sci., 13, 1127, 2013] concluded that TGF-associated neutrons produced by photonuclear reactions would cause serious hazard on the aircraft avionics. In this work, we will present detailed simulation-based estimations of effective doses received by humans that would be irradiated by TGFs for various production altitudes and distances from the TGF source.

  14. Dose perturbations by electromagnetic transponders in the proton environment.

    PubMed

    Dolney, Derek; McDonough, James; Vapiwala, Neha; Metz, James M

    2013-03-07

    Surgically implanted electromagnetic transponders have been used in external beam radiotherapy for target localization and position monitoring in real time. The effect of transponders on proton therapy dose distributions has not been reported. A Monte Carlo implementation of the transponder geometry is validated against film measurements in a proton SOBP and subsequently used to generate dose distributions for transponders at different positions and orientations in the proton SOBP. The maximum dose deficit is extracted in each case. Dose shadows of up to 60% occur for transponders positioned very near the end of range of the Bragg peak. However, if transponders are positioned further than 5 mm from the end of range, and are not oriented parallel to the beam direction, then the dose deficit can be kept below 10%.

  15. Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in A/J mice at low doses: a pilot study.

    PubMed

    Dahl, A R; Grossi, I M; Houchens, D P; Scovell, L J; Placke, M E; Imondi, A R; Stoner, G D; De Luca, L M; Wang, D; Mulshine, J L

    2000-08-01

    In previously treated head-and-neck cancer patients, p.o. administered isotretinoin (13-cis retinoic acid) reduced the occurrence of second aerodigestive tumors, including lung tumors, but side effects made chronic therapy problematic. We reasoned that inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity, and we proceeded with the pilot study reported here. Male A/J mice were given single i.p. doses of urethane, a common experimental lung carcinogen, or benzo[a]pyrene (BaP) or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), putative major carcinogens in tobacco smoke. The following day, exposures to isotretinoin aerosols for 45 min daily at 1.3, 20.7, or 481 microg/l were initiated. After 2 weeks, the high dose caused severe toxicity on the snout skin, necessitating a reduction of dose frequency to twice a week. As a precaution, the mid dose was reduced to three exposures per week. The weekly total deposited doses after the dose frequency reductions were calculated to be 0.24, 1.6, and 24.9 mg/kg for the low, mid, and high doses, of which 16% was estimated to be deposited in the lungs. The weekly deposited pulmonary drug doses were calculated to be 0.01, 0.07, and 1.1% of a previously reported ineffective oral dose in urethane-treated A/J mice. After 10-16 weeks, mice were sacrificed to count areas of pulmonary hyperplasia and adenomas. For all carcinogens, the mice exposed to the high isotretinoin dose showed reductions of tumor multiplicity ranging from 56 to 80% (P < 0.005). The mid dose was associated with reductions of tumor multiplicity by 67 and 88% (P < 0.005) in BaP- and NNK-treated mice, respectively, and was tolerated until approximately 12 weeks, when both these and the high-dose mice began losing weight. The low-dose mice had nonsignificant reductions of 30% (P < 0.13) and 16% (P < 0.30) for BaP- and NNK-treated mice, respectively without any evidence of side effects. For BaP- and

  16. Intensity-modulated radiosurgery: improving dose gradients and maximum dose using post inverse-optimization interactive dose shaping.

    PubMed

    Fuss, Martin; Salter, Bill J

    2007-06-01

    Intensity-modulated radiosurgery (IMRS) for brain metastases and arterio-venous malformations (AVM) using a serial tomotherapy system (Nomos Corp., Cranberry Township, PA) has been delivered in >150 cases over the last 5 years. A new software tool provided within the Corvus inverse planning software (ActiveRx) allows for post inverse planning re-optimization and individualization of the dose distribution. We analyzed this tool with respect to increasing the steepness of the dose gradient and in-target dose inhomogeneity while maintaining conformity. Fifteen clinically delivered IMRS plans for solitary brain metastases provided the basis for this analysis. The clinical IMRS plans were copied and the ActiveRx module was opened. The toolset in ActiveRx includes a hot spot eraser, a pencil tool to redefine isodose lines and a drag and drop tool, allowing reshaping of existing isodose lines. To assess changes in the steepness of the dose gradient and dose homogeneity, the 100%, 90%, 50% and 25% isodose volume, the volume of the target, maximum dose and mean dose to the target were recorded. We also recorded total monitor units and calculated treatment delivery times. Target volumes ranged from 0.6 to 14.1 cm(3) (mean/median 3.9/1.8 cm(3)). Mean RTOG conformity index (CI) of plans clinically delivered was 1.23+/-0.31; mean homogeneity index (HI) was 115+/-5%. After using the ActiveRx tool-set, the mean CI was slightly improved to 1.14+/-0.1, with an associated increase in HI to 141+/-10%. The average, respective Ian Paddick CI for the 100%, 90% 50% and 25% isodose lines were 0.79 vs. 0.83, 0.44 vs. 0.59, 0.12 vs. 0.19, and 0.04 vs. 0.07, representing significant improvements after using ActiveRx post-optimization. Total MU were reduced by a mean of 12.3% using ActiveRx, shortening estimated treatment delivery times by 3.2 minutes on average. A post inverse planning optimization tool for IMRS plans allowed for statistically significant improvements in the steepness of the

  17. Radiation dose implications of airborne contaminant deposition to humans.

    PubMed

    Andersson, K G; Fogh, C L; Byrne, M A; Roed, J; Goddard, A J H; Hotchkiss, S A M

    2002-02-01

    In nuclear accident consequence assessment, dose contributions from radionuclide deposition on the human body have in the past generally been either ignored or estimated on the basis of rather simple models. Recent experimental work has improved the state of knowledge of relevant processes and parameter ranges. The results presented in this paper represent a first approach to a detailed assessment of doses from radiopollutant deposition on the human body, based on contaminant-specific data. Both the dose to skin from beta-emitters and the whole-body dose from gamma-emitters on body surfaces were found to give potentially significant contributions to dose. Further, skin penetration of some contaminants could lead to significant internal doses.

  18. Radiation dose from cardiac computed tomography before and after implementation of radiation dose-reduction techniques.

    PubMed

    Raff, Gilbert L; Chinnaiyan, Kavitha M; Share, David A; Goraya, Tauqir Y; Kazerooni, Ella A; Moscucci, Mauro; Gentry, Ralph E; Abidov, Aiden

    2009-06-10

    Cardiac computed tomography angiography (CCTA) can accurately diagnose coronary artery disease, but radiation dose from this procedure is of concern. To determine whether a collaborative radiation dose-reduction program would be associated with reduced radiation dose in patients undergoing CCTA in a statewide registry over a 1-year period and to define its effect on image quality. A prospective, controlled, nonrandomized study conducted during a control period (July-August 2007), an intervention period (September 2007-April 2008), and a follow-up period (May-June 2008) at 15 hospital imaging centers participating in the Advanced Cardiovascular Imaging Consortium in Michigan, which included small community hospitals and large academic medical centers. A total of 4995 sequential patients undergoing CCTA for suspected coronary artery disease were enrolled; 4862 patients (97.3%) had complete radiation data for analysis. A best-practice CCTA scan model was used, which included minimized scan range, heart rate reduction, electrocardiographic-gated tube current modulation, and reduced tube voltage in suitable patients. Primary outcomes included dose-length product and effective radiation dose from all phases of the CCTA scan. Secondary outcomes were image quality assessed by a 4-point scale (1 indicated excellent; 2, good; 3, adequate; and 4, nondiagnostic) and frequency of diagnostic-quality scans. Compared with the control period, patients' estimated median radiation dose in the follow-up period was reduced by 53.3% (dose-length product decreased from 1493 mGy x cm [interquartile range {IQR}, 855-1823 mGy x cm] to 697 mGy x cm [IQR, 407-1163 mGy x cm]; P < .001) and effective dose from 21 mSv (IQR, 12-26 mSv) to 10 mSv (IQR, 6-16 mSv) (P < .001). The greatest reduction in dose occurred at low-volume sites. There were no significant changes in median image quality assessment during the control period compared with the follow-up period (median image quality of 2 [images

  19. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    threshold. However, low-dose and low-dose-rate induced adapted protection leads to hormetic type dose-response relationships (e.g. U or J shaped) for cancer induction. Indeed, our research findings point to several dose zones of biological responses: (1) The natural background radiation dose zone over which increasing background radiation doses appear to lead to decrease cancer risk (Transition Zone A) due to activation (in a stochastic manner) of a system of protective processes that include high-fidelity DNA repair, apoptosis of unstable cells, and immune system activation. (2) A dose zone just above natural background radiation exposure over which cancer risk appears to further decrease and then remain suppressed at a relatively constant level below the spontaneous frequency (Zone of Maximal Protection); (3) higher but moderate doses over which cancer risk increases rather steeply over relative narrow dose range (Transition Zone B) due to radiation related suppression of protective processes (immune system function and selective apoptosis of unstable cells); (4) higher doses (LNT zone) where cancer risk increases as a linear function of dose for a range of doses (protective processes maximally suppressed in this zone). The indicted dose zones are dose-rate and radiation-type dependent with the protective zone increasing as dose rate is decreases and exposure time extended. In fact, natural background low-LET radiation appears to be protecting us not only from cancer occurrence but also from other genomic instability associated diseases via repeatedly inducing transient adapted protection. Reducing natural background radiation exposure (e.g., via relocation) over extended periods (years) would be expected to cause more harm than benefit. The harm would be expressed as increased cases of cancer and other genomic-instability-associated diseases as well as in significantly reduced life expectancy.

  20. Quantification of Proton Dose Calculation Accuracy in the Lung

    SciTech Connect

    Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald

    2014-06-01

    Purpose: To quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC)–based dose calculation through measurements and to assess the clinical impact in a cohort of patients with tumors located in the lung. Methods and Materials: A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in the lung, and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm. Results: MC increased dose calculation accuracy in lung tissue compared with the TPS and reproduced dose measurements in the target to within ±2%. The average difference between measured and predicted dose in a plane through the center of the target was 5.6% for the TPS and 1.6% for MC. MC recalculations in patients showed a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors, MC also predicted consistently higher V5 and V10 to the normal lung, because of a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target could show large deviations, although this effect was highly patient specific. Range measurements showed that MC can reduce range uncertainty by a factor of ∼2: the average (maximum) difference to the measured range was 3.9 mm (7.5 mm) for MC and 7 mm (17 mm) for the TPS in lung tissue. Conclusion: Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. In addition, the ability to confidently reduce range margins would benefit all patients by potentially lowering toxicity.

  1. Estimated ultraviolet radiation doses in wetlands in six national parks

    USGS Publications Warehouse

    Diamond, S.A.; Trenham, P.C.; Adams, Michael J.; Hossack, B.R.; Knapp, R.A.; Stark, L.; Bradford, D.; Corn, P.S.; Czarnowski, K.; Brooks, P.D.; Fagre, D.B.; Breen, B.; Dentenbeck, N.E.; Tonnessen, K.

    2005-01-01

    Ultraviolet-B radiation (UV-B, 280–320-nm wavelengths) doses were estimated for 1024 wetlands in six national parks: Acadia (Acadia), Glacier (Glacier), Great Smoky Mountains (Smoky), Olympic (Olympic), Rocky Mountain (Rocky), and Sequoia/Kings Canyon (Sequoia). Estimates were made using ground-based UV-B data (Brewer spectrophotometers), solar radiation models, GIS tools, field characterization of vegetative features, and quantification of DOC concentration and spectral absorbance. UV-B dose estimates were made for the summer solstice, at a depth of 1 cm in each wetland. The mean dose across all wetlands and parks was 19.3 W-h m−2 (range of 3.4–32.1 W-h m−2). The mean dose was lowest in Acadia (13.7 W-h m−2) and highest in Rocky (24.4 W-h m−2). Doses were significantly different among all parks. These wetland doses correspond to UV-B flux of 125.0 μW cm−2 (range 21.4–194.7 μW cm−2) based on a day length, averaged among all parks, of 15.5 h. Dissolved organic carbon (DOC), a key determinant of water-column UV-B flux, ranged from 0.6 (analytical detection limit) to 36.7 mg C L−1 over all wetlands and parks, and reduced potential maximal UV-B doses at 1-cm depth by 1%–87 %. DOC concentration, as well as its effect on dose, was lowest in Sequoia and highest in Acadia (DOC was equivalent in Acadia, Glacier, and Rocky). Landscape reduction of potential maximal UV-B doses ranged from zero to 77% and was lowest in Sequoia. These regional differences in UV-B wetland dose illustrate the importance of considering all aspects of exposure in evaluating the potential impact of UV-B on aquatic organisms.

  2. Quantification of Proton Dose Calculation Accuracy in the Lung

    PubMed Central

    Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald

    2014-01-01

    Purpose Quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC) based dose calculation through measurements. Assess the clinical impact in a cohort of patients with tumors located in the lung. Methods A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in lung and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm. Results MC increases dose calculation accuracy in lung tissue compared to the TPS and reproduces dose measurements in the target to within ±2%. The average difference between measured and predicted dose in a plane through the center of the target is 5.6% for the TPS and 1.6% for MC. MC recalculations in patients show a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors MC also predicts consistently higher V5 and V10 to the normal lung, due to a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target can show large deviations, though this effect is very patient-specific. Range measurements show that MC can reduce range uncertainty by a factor ~2: the average(maximum) difference to the measured range is 3.9mm(7.5mm) for MC and 7mm(17mm) for the TPS in lung tissue. Conclusion Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. Additionally, the ability to confidently reduce range margins would benefit all patients through potentially lower toxicity. PMID:24726289

  3. Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium

    NASA Astrophysics Data System (ADS)

    Paiva Fonseca, Gabriel; Carlsson Tedgren, Åsa; Reniers, Brigitte; Nilsson, Josef; Persson, Maria; Yoriyaz, Hélio; Verhaegen, Frank

    2015-06-01

    Dose calculation in high dose rate brachytherapy with 192Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (Dm,m) and dose-to-water-in-medium (Dw,m). The relation between Dm,m and Dw,m for 192Ir is the main goal of this study, in particular the dependence of Dw,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: Dm,m, Dw,m (LCT), mean photon energy and photon fluence. Dw,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between Dm,m and Dw,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between Dw,m (SCT) and Dw,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between Dm,m and Dw,m (SCT) mainly depend on tissue type, differences between Dm,m and Dw,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources.

  4. Analysis of occupational doses of workers on the dose registry of the Federal Radiation Protection Service in 2000 and 2001.

    PubMed

    Ogundare, F O; Balogun, F A

    2003-01-01

    In 2000 and 2001 about 279 and 221 radiation workers, respectively, were monitored by the Federal Radiation Protection Service, University of Ibadan, in Nigeria. The distribution of the occupational doses shows that the majority of workers received doses below 4 mSv in each of the two years. The radiation workers in the two years are classified into two occupational categories: medicine and industry. The mean annual effective doses, collective doses and the collective dose distribution ratios for workers in each category and the entire monitored workers were calculated. The mean annual effective doses were compared with their corresponding worldwide values quoted by UNSCEAR. In each of the two years, a few workers in industry received doses higher than 50 mSv. The collective dose distribution ratio was found to be about 0.49, which is very close to the highest value of 0.5 in the range of values considered by UNSCEAR as normal for this parameter. This suggests that extra measures have to be taken, particularly in industry, to ensure that the proportion of workers at risk does not go outside this normal range. The occupational doses were also modelled by both the log-normal and Weibull distributions. Both distributions were found to describe the data in almost the same way.

  5. Low- vs. standard-dose coronary artery calcium scanning.

    PubMed

    Hecht, Harvey S; de Siqueira, Maria Eduarda Menezes; Cham, Matthew; Yip, Rowena; Narula, Jagat; Henschke, Claudia; Yankelevitz, David

    2015-04-01

    This study was designed to assess the accuracy of coronary artery calcium scans (CACS) acquired at radiation doses below mammography and low-dose lung scanning, compared with standard-dose CACS. CACS was performed in 102 consecutive patients at 120 kVp; all were imaged at standard-dose mAs levels ranging from 30 to 80 mAs determined by their weight, with iterative reconstruction (IR) level 3, and at 50% of the standard-dose mAs with IR level 7 to compensate for the expected increased noise with lower mAs. The low- vs. standard-dose mAs was 24.5 ± 8.8 vs. 48.5 ± 17.8 mAs (P < 0.0001), and the radiation exposure was 0.37 ± 0.16 vs. 0.76 + 0.34 mSv (P < 0.0001). The Agatston score correlation between the low and high dose was excellent (r = 0.998, P < 0.0001) over a range of scores from 0 to 2512. The weighted kappa for agreement of standard CAC risk categories was 0.95 (95% CI 0.83-0.97). The mean of the differences between individual low- and standard-dose Agatston scores was 17.4 ± 25.8, lower than the reported variability of two scans performed with the same mAs. There was excellent agreement of CACS-based risk classification at low and standard doses, with lower interscan variability than with reported identical doses. The low-dose CACS radiation exposure was less than the approved screening tools of mammography and low-dose lung scanning. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  6. Errors and Uncertainties in Dose Reconstruction for Radiation Effects Research

    SciTech Connect

    Strom, Daniel J.

    2008-04-14

    Dose reconstruction for studies of the health effects of ionizing radiation have been carried out for many decades. Major studies have included Japanese bomb survivors, atomic veterans, downwinders of the Nevada Test Site and Hanford, underground uranium miners, and populations of nuclear workers. For such studies to be credible, significant effort must be put into applying the best science to reconstructing unbiased absorbed doses to tissues and organs as a function of time. In many cases, more and more sophisticated dose reconstruction methods have been developed as studies progressed. For the example of the Japanese bomb survivors, the dose surrogate “distance from the hypocenter” was replaced by slant range, and then by TD65 doses, DS86 doses, and more recently DS02 doses. Over the years, it has become increasingly clear that an equal level of effort must be expended on the quantitative assessment of uncertainty in such doses, and to reducing and managing uncertainty. In this context, this paper reviews difficulties in terminology, explores the nature of Berkson and classical uncertainties in dose reconstruction through examples, and proposes a path forward for Joint Coordinating Committee for Radiation Effects Research (JCCRER) Project 2.4 that requires a reasonably small level of effort for DOSES-2008.

  7. Single dose pharmacokinetics and tolerance of pancopride in healthy volunteers.

    PubMed

    Dewland, P; Pérez Campos, A; Martinez-Tobed, A

    1995-02-01

    Pancopride (LAS 30451, CAS 121650-80-4) is a new selective 5-hydroxytryptamine3 receptor antagonist which has demonstrated antiemetic properties in animal models. The tolerance and pharmacokinetics of pancopride and its effect on the 5-hydroxytryptamine flare test were examined in healthy male volunteers, in three single-dose studies. The studies consisted of two rising dose tolerance and kinetic studies with placebo control, each involving 14 volunteers, and an absolute bioavailability study involving 12 volunteers. The doses used in the rising dose studies were 0.5-20 mg intravenous pancopride in the first study, and 5-40 mg pancopride as oral solution in the second study. For the absolute bioavailability study, 20 mg doses as intravenous infusion, oral tablet and oral solution were compared. Pancopride was well tolerated at these doses in these studies. There were no significant effects on pulse rate, blood pressure, or electrocardiograms, or on haematology or serum biochemistry. Few adverse events were recorded, the most significant being gastrointestinal effects (including diarrhoea and soft stools) seen particularly with the 40 mg oral dose. Pharmacokinetic parameters for the 24 h after dosing were derived from plasma and urine pancopride levels, determined using a capillary gas chromatography-mass spectrometry method. Linear kinetics appeared to apply over the intravenous dose range 5-20 mg. Urinary recovery of unchanged pancopride was in the order of 10-17% over the 24 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Survey of computed tomography scanners in Taiwan: Dose descriptors, dose guidance levels, and effective doses

    SciTech Connect

    Tsai, H. Y.; Tung, C. J.; Yu, C. C.; Tyan, Y. S.

    2007-04-15

    The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinations was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.

  9. Collective dose-practical ways to estimate a dose matrix.

    PubMed

    Simmonds, Jane; Sihra, Kamaljit; Bexon, Antony

    2006-06-01

    It has been suggested that collective doses should be presented in the form of a 'dose matrix' giving information on the breakdown of collective dose in space and time and by population group. This paper is an initial attempt to provide such a breakdown by geographic region and time, and to give an idea of associated individual doses for routine discharges to atmosphere. This is done through the use of representative per-caput individual doses but these need to be supplemented by information on the individual doses received by the critical group for a full radiological impact assessment. The results show that it is important to distinguish between the different population groups for up to a few hundred years following the discharge. However, beyond this time the main contribution is from global circulation and this distinction is less important. The majority of the collective dose was found to be delivered at low levels of individual doses; the estimated per-caput dose rates were significantly less than 10(-5) Sv y(-1), a level of dose felt to give rise to a trivial risk to the exposed individual.

  10. Standardized radiological dose evaluations

    SciTech Connect

    Peterson, V.L.; Stahlnecker, E.

    1996-05-01

    Following the end of the Cold War, the mission of Rocky Flats Environmental Technology Site changed from production of nuclear weapons to cleanup. Authorization baseis documents for the facilities, primarily the Final Safety Analysis Reports, are being replaced with new ones in which accident scenarios are sorted into coarse bins of consequence and frequency, similar to the approach of DOE-STD-3011-94. Because this binning does not require high precision, a standardized approach for radiological dose evaluations is taken for all the facilities at the site. This is done through a standard calculation ``template`` for use by all safety analysts preparing the new documents. This report describes this template and its use.

  11. New model for assessing dose, dose rate, and temperature sensitivity of radiation-induced absorption in glasses

    SciTech Connect

    Gilard, Olivier; Quadri, Gianandrea; Caussanel, Matthieu; Duval, Herve; Reynaud, Francois

    2010-11-15

    A new theoretical approach is proposed to explain the dose, dose rate and temperature sensitivity of the radiation-induced absorption (RIA) in glasses. In this paper, a {beta}{sup th}-order dispersive kinetic model is used to simulate the growth of the density of color centers in irradiated glasses. This model yields an explanation for the power-law dependence on dose and dose rate usually observed for the RIA in optical fibers. It also leads to an Arrhenius-like relationship between the RIA and the glass temperature during irradiation. With a very limited number of adjustable parameters, the model succeeds in explaining, with a good agreement, the RIA growth of two different optical fiber references over wide ranges of dose, dose rate and temperature.

  12. Dose assessment of an accidental exposure at the IPNS

    SciTech Connect

    Campos Torres, M.M.

    1995-02-01

    Seven different methods were used to estimate the dose rate to a female worker who was accidentally exposed in the neutron PHOENIX beamline at the IPNS. Theoretical and measured entrance dose ranged from 550 mrem/min to 2850 mrem/min. Theoretical estimates were based on a Monte Carlo simulation of a spectrum provided by IPNS (Crawford Spectrum). Dose measurements were made with TLDs on phantoms and with ionization chambers in a water phantom. Estimates of the whole body total effective dose equivalent (TEDE) rate ranged from 5.2 mrem/min to 840 mrem/min. Assumed and measured quality factors ranged from 2.6 to 11.8. Cytogenetic analyses of blood samples detected no positive exposure. The recommended TEDE rate was 158 mrem/min. The TEDE was 750 mrem.

  13. Dose assessment of an accidental exposure at IPNS

    SciTech Connect

    Torres, M.M.C.

    1996-05-01

    Seven different methods were used to estimate the dose rate to a female worker who was accidentally exposed in the neutron PHOENIX beamline at the IPNS. Theoretical and measured entrance dose rates ranged from 550 mrem/min to 2,850 mrem/min. Theoretical estimates were based on a Monte Carlo simulation of a spectrum provided by IPNS (Crawford Spectrum). Dose measurements were made with TLDs on phantoms and with ionization chambers in a water phantom. Estimates of the whole body total effective dose equivalent (TEDE) rate ranged from 5.2 mrem/min to 840 mrem/min. Assumed and measured quality factors ranged from 2.6 to 11.8. Cytogenic analyses of blood samples detected no positive exposure. The recommended TEDE rate was 158 mrem/min. The TEDE was 750 mrem.

  14. Mammography-oncogenecity at low doses.

    PubMed

    Heyes, G J; Mill, A J; Charles, M W

    2009-06-01

    Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 +/- 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 +/- 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low

  15. Computing effective dose in cardiac CT

    NASA Astrophysics Data System (ADS)

    Huda, Walter; Tipnis, Sameer; Sterzik, Alexander; Schoepf, U. Joseph

    2010-07-01

    We present a method of estimating effective doses in cardiac CT that accounts for selected techniques (kV mAs-1), anatomical location of the scan and patient size. A CT dosimetry spreadsheet (ImPACT CT Patient Dosimetry Calculator) was used to estimate effective doses (E) using ICRP 103 weighting factors for a 70 kg patient undergoing cardiac CT examinations. Using dose length product (DLP) for the same scans, we obtained values of E/DLP for three CT scanners used in cardiac imaging from two vendors. E/DLP ratios were obtained as a function of the anatomical location in the chest and for x-ray tube voltages ranging from 80 to 140 kV. We also computed the ratio of the average absorbed dose in a water cylinder modeling a patient weighing W kg to the corresponding average absorbed dose in a water cylinder equivalent to a 70 kg patient. The average E/DLP for a 16 cm cardiac heart CT scan was 26 µSv (mGy cm)-1, which is about 70% higher than the current E/DLP values used for chest CT scans (i.e. 14-17 µSv (mGy cm)-1). Our cardiac E/DLP ratios are higher because the cardiac region is ~30% more radiosensitive than the chest, and use of the ICRP 103 tissue weighting factors increases cardiac CT effective doses by ~30%. Increasing the x-ray tube voltage from 80 to 140 kV increases the E/DLP conversion factor for cardiac CT by 17%. For the same incident radiation at 120 kV, doses in 45 kg adults were ~22% higher than those in 70 kg adults, whereas doses in 120 kg adults were ~28% lower. Accurate estimates of the patient effective dose in cardiac CT should use ICRP 103 tissue weighting factors, and account for a choice of scan techniques (kV mAs-1), exposed scan region, as well as patient size.

  16. A silicon strip detector dose magnifying glass for IMRT dosimetry

    SciTech Connect

    Wong, J. H. D.; Carolan, M.; Lerch, M. L. F.; Petasecca, M.; Khanna, S.; Perevertaylo, V. L.; Metcalfe, P.; Rosenfeld, A. B.

    2010-02-15

    Purpose: Intensity modulated radiation therapy (IMRT) allows the delivery of escalated radiation dose to tumor while sparing adjacent critical organs. In doing so, IMRT plans tend to incorporate steep dose gradients at interfaces between the target and the organs at risk. Current quality assurance (QA) verification tools such as 2D diode arrays, are limited by their spatial resolution and conventional films are nonreal time. In this article, the authors describe a novel silicon strip detector (CMRP DMG) of high spatial resolution (200 {mu}m) suitable for measuring the high dose gradients in an IMRT delivery. Methods: A full characterization of the detector was performed, including dose per pulse effect, percent depth dose comparison with Farmer ion chamber measurements, stem effect, dose linearity, uniformity, energy response, angular response, and penumbra measurements. They also present the application of the CMRP DMG in the dosimetric verification of a clinical IMRT plan. Results: The detector response changed by 23% for a 390-fold change in the dose per pulse. A correction function is derived to correct for this effect. The strip detector depth dose curve agrees with the Farmer ion chamber within 0.8%. The stem effect was negligible (0.2%). The dose linearity was excellent for the dose range of 3-300 cGy. A uniformity correction method is described to correct for variations in the individual detector pixel responses. The detector showed an over-response relative to tissue dose at lower photon energies with the maximum dose response at 75 kVp nominal photon energy. Penumbra studies using a Varian Clinac 21EX at 1.5 and 10.0 cm depths were measured to be 2.77 and 3.94 mm for the secondary collimators, 3.52 and 5.60 mm for the multileaf collimator rounded leaf ends, respectively. Point doses measured with the strip detector were compared to doses measured with EBT film and doses predicted by the Philips Pinnacle treatment planning system. The differences were 1

  17. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    SciTech Connect

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2008-01-15

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 {mu}g g{sup -1}. Linear regression of whole tooth lead ({mu}g g{sup -1}) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r{sup 2}=0.647 (p<0.0001). Laser ablation inductively coupled plasma mass spectrometry was employed to determine lead content at micrometer scale spatial resolution in the teeth of seven goats representing the dosing range. Highly localized concentrations of lead, ranging from about 10 to 2000 {mu}g g{sup -1}, were found in circumpulpal dentine. Linear regression of circumpulpal lead ({mu}g g{sup -1}) on cumulative lead dose (g) yielded a slope of 23 with r{sup 2}=0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats.

  18. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    PubMed Central

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2013-01-01

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g−1. Linear regression of whole tooth lead (μg g−1) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r2 = 0.647 (p<0.0001). Laser ablation inductively coupled plasma mass spectrometry was employed to determine lead content at micrometer scale spatial resolution in the teeth of seven goats representing the dosing range. Highly localized concentrations of lead, ranging from about 10 to 2000 μg g−1, were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g−1) on cumulative lead dose (g) yielded a slope of 23 with r2 = 0.961 (p = 0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats. PMID:17644083

  19. CT effective dose per dose length product using ICRP 103 weighting factors

    SciTech Connect

    Huda, Walter; Magill, Dennise; He Wenjun

    2011-03-15

    Purpose: To generate effective dose per unit dose length product (E/DLP) conversion factors incorporating ICRP Publication 103 tissue weighting factors. Methods: Effective doses for CT examinations were obtained using the IMPACT Dosimetry Calculator using all 23 dose data sets that are offered by this spreadsheet. CT examinations were simulated for scans performed along the patient long axis for each dosimetry data set using a 4 cm beam width ranging from the upper thighs to top of the head. Five basic body regions (head, neck, chest, abdomen, and pelvis), as well as combinations of the regions (head/neck, chest/abdomen, abdomen/pelvis, and chest/abdomen/pelvis) and whole body CT scans were investigated. Correction factors were generated that can be applied to convert E/DLP conversion factors based on ICRP 60 data to conversion factors that are valid for ICRP 103 data (i.e., E{sub 103}/E{sub 60}). Results: Use of ICRP 103 weighting factors increase effective doses for head scans by {approx}11%, for chest scans by {approx}20%, and decrease effective doses for pelvis scans by {approx}25%. Current E/DLP conversion factors are estimated to be 2.4 {mu}Sv/mGy cm for head CT examinations and range between 14 and 20 {mu}Sv/mGy cm for body CT examinations. Conclusions: Factors that enable patient CT doses to be adjusted to account for ICRP 103 tissue weighting factors are provided, which result in E/DLP factors that were increased in head and chest CT, reduced in pelvis CT, and showed no marked change in neck and abdomen CT.

  20. Low Dose Ionizing Radiation Modulates Immune Function

    SciTech Connect

    Nelson, Gregory A.

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  1. A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT

    NASA Astrophysics Data System (ADS)

    Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.

    2012-04-01

    While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4

  2. A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT.

    PubMed

    Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B

    2012-04-07

    While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4

  3. A comprehensive study on the relationship between image quality and imaging dose in low-dose cone beam CT

    PubMed Central

    Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.

    2012-01-01

    While compressed sensing (CS) based algorithms have been developed for low-dose cone beam CT (CBCT) reconstruction, a clear understanding on the relationship between the image quality and imaging dose at low dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding on the tradeoff between image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image guided radiation therapy (IGRT). Main findings of this work include: 1) Under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40–100 total mAs, depending on the specific IGRT applications. 2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. 3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. 4) The clinically

  4. The susceptibility of TaOx-based memristors to high dose rate ionizing radiation and total ionizing dose

    DOE PAGES

    McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

    2014-11-11

    This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaOx) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×107 rad(Si)/s to 4.7 ×108 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×108 rad(Si)/s. This is the first dose rate study on any type of memristive memory technology. Inmore » addition to assessing the tolerance of TaOx memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

  5. Effects of dose and dose protraction on embryotoxicity of 14.1 MeV neutron irradiation in rats

    SciTech Connect

    Beckman, D.A.; Buck, S.J. |; Solomon, H.M.; Gorson, R.O.; Mills, R.E.; Brent, R.L. |

    1994-06-01

    The embryotoxic effects of neutron radiation on rodent embryos are documented, but there is disagreement about the dose-response relationship and the impact of protracting the dose. Pregnant rats were exposed to total absorbed doses of 0.15 to 1.50 Gy 14.1 MeV neutrons on day 9.5 after conception, coincident with the most sensitive stage of embryonic development for the induction of major congenital malformations. In general terms, the incidence of embryotoxic effects increased with increasing total absorbed dose. However, the dose-response relationship differed depending on the parameter of embryotoxicity chosen, namely, intrauterine death, malformations or very low body weight. In a second study, embryos were exposed to a single embryotoxic absorbed dose (0.75 Gy) administered at a range of dose rates, from 0.10 to 0.50 Gy/h. The results offer no evidence that protraction of this selected dose significantly increased or decreased the incidence or pattern of embryotoxicity of the neutron exposure used in this study. The results do not support the hypothesis of a linear dose-response relationship for the effects of prenatal neutron irradiation that contribute to embryotoxicity for total absorbed doses of 0.15 to 1.50 Gy. 23 refs., 8 tabs.

  6. Measuring pacemaker dose: A clinical perspective

    SciTech Connect

    Studenski, Matthew T.; Xiao Ying; Harrison, Amy S.

    2012-07-01

    Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.

  7. Phenytoin dose adjustment in epileptic patients

    PubMed Central

    Mawer, G. E.; Mullen, P. W.; Rodgers, Margaret; Robins, A. J.; Lucas, S. B.

    1974-01-01

    1 A preliminary survey showed that many outpatients with partially controlled epilepsy had serum concentrations of phenytoin below the recommended therapeutic range (10-20 μg/ml). A phenytoin tolerance test was devised with the intention of predicting a more adequate daily dose for such a patient. 2 Fifteen patients were each given an oral test dose of 600 mg phenytoin sodium and the serum concentration of phenytoin was measured at intervals over 48 h; the concentration rose during the first 4 h and decayed between 12-48 h as an almost linear function of time. 3 The serum concentration/time curves were fitted by an interative computer program based on the Michaelis-Menten equation. The mean saturated rate of elimination of phenytoin was 435 mg/day and the serum concentration (Km) corresponding with 50% saturation was 3.8 μg/ml. The mean calculated dose of phenytoin sodium required for a steady state serum concentration of 10-20 μg/ml was 345-400 mg/day. 4 The Michaelis-Menten principle was used to predict steady state serum phenytoin concentrations in individual patients receiving daily doses of phenytoin sodium adjusted by steps of 100 mg. The serum concentrations tended to be either too low or too high. The steep relationship between phenytoin concentration and dose indicates that when the concentration reaches 5-10 μg/ml it is then appropriate to adjust dose by small steps of about 25 mg. PMID:22454904

  8. Phenytoin dose adjustment in epileptic patients.

    PubMed

    Mawer, G E; Mullen, P W; Rodgers, M; Robins, A J; Lucas, S B

    1974-04-01

    1 A preliminary survey showed that many outpatients with partially controlled epilepsy had serum concentrations of phenytoin below the recommended therapeutic range (10-20 μg/ml). A phenytoin tolerance test was devised with the intention of predicting a more adequate daily dose for such a patient. 2 Fifteen patients were each given an oral test dose of 600 mg phenytoin sodium and the serum concentration of phenytoin was measured at intervals over 48 h; the concentration rose during the first 4 h and decayed between 12-48 h as an almost linear function of time. 3 The serum concentration/time curves were fitted by an interative computer program based on the Michaelis-Menten equation. The mean saturated rate of elimination of phenytoin was 435 mg/day and the serum concentration (K(m)) corresponding with 50% saturation was 3.8 μg/ml. The mean calculated dose of phenytoin sodium required for a steady state serum concentration of 10-20 μg/ml was 345-400 mg/day. 4 The Michaelis-Menten principle was used to predict steady state serum phenytoin concentrations in individual patients receiving daily doses of phenytoin sodium adjusted by steps of 100 mg. The serum concentrations tended to be either too low or too high. The steep relationship between phenytoin concentration and dose indi